Genetic Testing Updated June 19, 2026

MRD Testing and Medicare Coverage: Why 'Covered' Depends Entirely on the Cancer and the Question Being Asked

Medicare covers molecular residual disease testing, but not as a blanket assay benefit. Coverage is granted indication by indication through MolDX Local Coverage Determinations, and getting paid depends on matching the exact cancer, stage, and clinical use the current policy describes.

A patient finishes adjuvant chemotherapy for stage III colon cancer. Their oncologist wants to know, before scans would ever show anything, whether there is still cancer circulating in the bloodstream. So they order a molecular residual disease test. Months later, your lab is staring at a denial, or the oncology practice is staring at a surprise bill, and the question everyone asks is the same one that opened this paragraph in reverse: wasn't this covered?

The honest answer is that "covered" is the wrong unit of analysis for MRD testing. Medicare does cover it. But coverage attaches to a specific cancer, a specific stage, and a specific clinical question, and a claim that drifts even slightly off those coordinates gets denied no matter how clinically reasonable the order was. If you run, own, or manage revenue for a lab or oncology practice that touches these assays, the difference between a paid claim and a write-off usually lives in that gap.

Disclaimer: This article is educational and is not medical, legal, billing, or coverage advice. It is not a coverage determination for any patient or claim. Coverage policies change frequently, Medicare Administrative Contractors apply their own local policies, and the only authoritative sources are the current LCDs, articles, and manufacturer billing guidance themselves. Treat every figure and criterion here as "true as of the cited date — verify the current policy." Consult qualified clinical, billing, and compliance professionals before making coverage, treatment, or billing decisions. Use this information at your own risk.

What MRD testing actually is, and why coverage is awkward

Molecular residual disease testing — also called minimal residual disease testing — looks for tiny amounts of tumor-derived circulating tumor DNA (ctDNA) in a blood sample after a patient has been treated for cancer. The premise is that ctDNA can flag residual or recurrent disease earlier and more specifically than imaging or traditional protein markers. Several assays compete in this space — among them Natera's Signatera, Guardant Health's Guardant Reveal, and Exact Sciences' Oncodetect — and they differ in important ways, some tumor-informed (designing a personalized panel from the patient's own tumor tissue), others tumor-naive.

Here is what makes coverage awkward. MRD is not one test for one purpose. The same blood draw might be used to stratify recurrence risk right after surgery, to decide whether a patient needs adjuvant chemotherapy, to monitor for recurrence over years of surveillance, or to watch whether a tumor is responding to immunotherapy. Each of those is a different clinical claim, supported by different evidence, in a different patient population. Medicare does not pay for "an MRD test." It pays for an MRD test used for a purpose it has decided is reasonable and necessary, in a patient who fits the population the evidence supports.

That is why there is no single national yes-or-no for MRD. There is a stack of indication-specific decisions, and they are made mostly at the contractor level.

How MRD gets covered: MolDX and the LCD

Most molecular diagnostic coverage in Medicare flows through the MolDX program, administered by Palmetto GBA and operating across several Medicare Administrative Contractors (including Noridian and others). MolDX doesn't issue one blanket rule for ctDNA. Instead, it publishes Local Coverage Determinations — LCDs — that define, in clinical detail, when a particular class of test is covered for a particular use.

The practical consequence is that MRD coverage is best understood as a portfolio of indications that grows over time, each added when MolDX is persuaded the evidence supports it, and applied test by test as individual assays qualify. A use can be covered for one cancer and not another, or for recurrence monitoring but not a different use, all under the same program. This is the single most important mental model for anyone trying to get these claims paid: you are never asking "is this test covered?" You are asking "is this test, for this cancer, at this stage, used for this purpose, covered under the current LCD?"

The colorectal pathway: the template everything else followed

Colorectal cancer is where MRD coverage was first established, and it remains the most mature pathway, so it is the template worth understanding.

MolDX opened the door in 2020 with a colorectal MRD policy, now reflected in LCD L38290. The first assay to secure coverage under it was Natera's Signatera, through a final Noridian decision effective October 18, 2020 — but the more durable point is what the policy actually covered, not which test got there first. It covered two distinct uses at once: post-resection risk stratification, using ctDNA status to inform adjuvant treatment decisions, and ongoing surveillance for recurrence in patients who had no evidence of disease but remained at risk.

The surveillance piece carries a detail that operators repeatedly trip over. The MolDX colorectal policy doesn't authorize unlimited monitoring. It ties allowable testing frequency to the schedule for CEA (carcinoembryonic antigen) surveillance under NCCN guidelines, within roughly a one-month timing window, according to the language in the CMS Medicare Coverage Database. In other words, Medicare anchored MRD monitoring frequency to an existing, familiar surveillance cadence rather than letting it run open-ended. If you bill serial MRD tests more often than the policy contemplates, expect those extra claims to be denied even though the patient is squarely in the covered population.

The colorectal policy also illustrates why payers moved at all. These LCDs rest on clinical-utility evidence that ctDNA can flag recurrence earlier and more specifically than imaging or protein markers like CEA — exactly the kind of argument that moves a coverage determination from "promising" to "reasonable and necessary." (Treat any specific performance figures you encounter, from any assay maker, as the studies' and manufacturers' reported results rather than a guarantee for any patient.)

Expansion: more cancers, and a different question entirely

Once the colorectal template existed, the story became one of expansion — both to new tumor types and to a genuinely different clinical use.

On the tumor-type side, MolDX's broader MRD-for-cancer LCD (L38779) describes covered uses well beyond colorectal, spanning breast, bladder, ovarian, and lung cancer. Individual assays qualify under that policy on their own timelines; Natera, for example, reported Signatera's coverage under L38779 in mid-2025. The pattern is exactly the indication-by-indication accretion described above: each cancer arrives as its own covered use, on its own schedule, supported by its own evidence.

The more conceptually interesting expansion is immunotherapy response monitoring, which the broader LCD also addresses as a pan-cancer use — reading ctDNA dynamics during treatment as a signal of whether a patient is responding. That is a different clinical question from "is there residual disease after surgery?" It is "is this drug working?" The fact that Medicare extended coverage into response monitoring shows how the same underlying technology can earn separate coverage for separate uses, and it is a reminder that you cannot assume an assay covered for post-surgical surveillance is also covered for therapy monitoring, or vice versa. The use case is part of what is being covered.

Coverage is assay-specific, not category-wide

A trap worth naming explicitly: coverage attaches to assays, not to the category. The fact that one MRD test is covered for colorectal cancer tells you nothing definitive about whether another lab's test is covered for the same patient.

The competitive landscape makes this concrete, and it is genuinely multi-vendor. Guardant Health announced Medicare coverage for Guardant Reveal — a tissue-free, methylation-based ctDNA test — for colorectal cancer surveillance after curative-intent treatment (Guardant press release, January 2025). Exact Sciences announced Medicare coverage for its Oncodetect MRD test for serial use in stage II, III, and resectable stage IV colorectal cancer, in both the adjuvant and recurrence-monitoring settings (Exact Sciences press release, July 2025). Natera's Signatera, as noted above, carries its own set of covered indications. Each of these is a separate coverage decision, with its own criteria, populations, and effective dates.

For an operator, the implication is operational, not academic. If your lab runs more than one MRD assay, or if an ordering practice sends specimens to multiple labs, you cannot maintain a single mental rule for "MRD coverage." You need the current criteria for each assay you bill. Mixing them up — applying one test's covered stages to another test's claim — is a clean path to denials.

What this means for getting paid

Step back from the individual policies and the operating reality comes into focus. MRD reimbursement is a moving target with several independent axes, and a claim has to land correctly on every one of them:

  • The cancer type must be one the current LCD covers for that assay.
  • The stage and clinical setting must match the covered population — post-resection risk stratification, surveillance, neoadjuvant, response monitoring, and so on are not interchangeable.
  • The clinical use must be a covered use; an assay covered for residual-disease surveillance is not automatically covered for immunotherapy monitoring.
  • The frequency of serial testing must stay within what the policy allows, which for colorectal surveillance is pegged to the CEA schedule.
  • The documentation and ordering must establish that the patient actually meets those criteria, because coverage in principle is not a payable claim — that's true across molecular diagnostics, and it's true here.

None of these axes is static. New cancers get added. New assays gain coverage. Frequency language and covered settings get revised as policies are updated and replaced. A coverage fact that was accurate when a billing protocol was written can quietly go stale, and the first sign is often a denial that nobody can immediately explain.

That's the real lesson buried in the MRD story. The clinical case for these tests keeps getting stronger and coverage keeps expanding — which sounds like unambiguously good news, but it means the rules you have to track are multiplying, not consolidating. For a lab or oncology practice, sustainable MRD revenue isn't a one-time exercise of confirming "this MRD test is covered." It's the ongoing discipline of knowing, for each assay and each indication you bill, what the current policy actually says, and noticing the moment it changes.

That is the category Converus works in: keeping payer coverage rules current per test and per indication, so the gap between "clinically appropriate" and "actually paid" doesn't quietly become a write-off. The MRD landscape is simply one of the clearest examples of why that gap exists in the first place.

As always, treat the specifics above as accurate to their cited dates and verify the current applicable LCD, article, and the assay maker's billing guidance before you rely on any coverage statement for a real claim.

Sources

Frequently Asked Questions

Does Medicare cover MRD (molecular residual disease) testing?
Yes, but only for specific cancers and clinical uses defined in MolDX Local Coverage Determinations (LCDs), not as a blanket benefit. Colorectal cancer was the first covered pathway, established in 2020, and coverage has since expanded to additional cancers and to several different MRD assays, each on its own terms. It remains both indication-specific and assay-specific, so check the current applicable LCD before relying on it.
Which cancers does Medicare cover MRD testing for?
It depends on the assay and the current LCD. MolDX's broader MRD-for-cancer LCD (L38779) describes covered uses spanning colorectal, breast, bladder, ovarian, and lung cancer, plus pan-cancer immunotherapy monitoring, but a given assay is only covered once it qualifies under the policy. Because covered indications are added over time and differ by test, verify the specific cancer type, clinical use, and assay in the current policy rather than assuming MRD is covered across all tumors.
How often will Medicare pay for serial MRD testing?
MolDX colorectal cancer policy ties allowable testing frequency to the schedule for CEA surveillance under NCCN guidelines (within roughly a one-month timing window), per the CMS Medicare Coverage Database. Frequency limits are part of the coverage criteria, so testing more often than the policy allows is a common reason serial-monitoring claims are denied. Confirm the frequency language in the LCD that applies to the patient's indication.
Does Medicare coverage of one MRD test apply to the others?
No. Coverage is assay-specific. Several MRD tests have secured Medicare coverage on their own timelines, including Natera's Signatera, Guardant Health's Guardant Reveal (colorectal surveillance, January 2025), and Exact Sciences' Oncodetect (stage II, III, and resectable stage IV colorectal cancer, July 2025). Each has its own criteria, populations, and effective dates, so coverage of one MRD assay does not imply coverage of another.
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