MolDX's New Hematologic Malignancy NGS Coverage Policies: What Labs Need to Know
Short answer: On August 21, 2026, MolDX posted three proposed LCDs — covering NGS for hematologic malignancies, genome-wide detection of copy number/structural variants in blood cancers, and transcriptional biomarkers for renal carcinoma — simultaneously through Palmetto GBA, CGS, and Noridian. The first two lean toward coverage with tight clinical criteria; the renal biomarker policy proposes non-coverage. Comment periods are open now.
Three Proposed LCDs, One Day, Three MACs
MolDX, the molecular diagnostics program CMS contractors use to evaluate lab-developed tests, posted three new proposed Local Coverage Determinations on August 21, 2026. Each was issued in parallel by the three MolDX-participating Medicare Administrative Contractors — Palmetto GBA, CGS Administrators, and Noridian Healthcare Solutions — meaning the same draft policy language now governs Medicare Part B coverage decisions across most of the country at once (Discoveries in Health Policy).
The three drafts are: DL40425 (Palmetto), DL40451 (CGS), and DL40427 (Noridian) — "Next-Generation Sequencing for Hematologic Malignancies and Suspected Hematologic Malignancies"; DL40407/DL40431/DL40411 — "Genome-Wide Molecular Methodologies for the Detection of Copy Number Alterations and Structural Variants in Hematologic Neoplasms"; and DL40429/DL40433/DL40435 — "Transcriptional Biomarkers for Therapeutic Decision-Making in Renal Carcinoma" (CMS Medicare Coverage Database). This synchronized, multi-MAC posting pattern is consistent with ongoing pressure on CMS to consolidate MolDX policy nationally — a push payers like Blue Cross have made publicly this year.
Hematologic Malignancy NGS: Coverage Tied to Clinical Decision Points
DL40425 proposes conditional coverage for multigene NGS panels used in confirmed or suspected hematologic malignancies, but only at three clinical decision points: initial diagnosis, suspected disease progression or transformation, and confirmed clinical relapse. Coverage requires that results be necessary either for WHO/ICC classification or to drive an immediate management decision — targeted therapy selection, treatment-intensity adjustment, or stem-cell transplant eligibility (Discoveries in Health Policy).
The policy explicitly excludes solid tumor testing, circulating tumor DNA assays, germline testing, and minimal residual disease (MRD) monitoring — labs running combined panels will need to separate those use cases for billing purposes. The companion draft billing article, DA60490, lists 356 supporting ICD-10-CM diagnosis codes spanning follicular and diffuse large B-cell lymphomas, mantle cell lymphoma, acute and chronic leukemias, multiple myeloma, myelodysplastic syndromes, and Langerhans-cell histiocytosis, and requires a DEX Z-Code identifier in the claim narrative alongside the appropriate CPT/PLA code (CMS Draft Article DA60490).
One detail RCM teams should flag now: the draft article states that multiple claims for the same beneficiary billed within a six-month window may be suspended for review, since the LCD only supports testing at those three defined decision points — not routine re-testing.
Genome-Wide CNA/SV Detection: A Path Beyond Karyotyping
DL40407 addresses a broader shift already underway in hematopathology labs: replacing bundles of individual cytogenetic tests (karyotype, FISH panels, chromosomal microarray) with a single genome-wide workflow. The proposed LCD recognizes whole genome sequencing, optical genome mapping, and genomic proximity mapping as potentially meeting that bar, with limited positive coverage when results inform guideline-based diagnosis or management of hematologic neoplasms. Bionano Genomics confirmed the proposed policy directly addresses optical genome mapping for structural variant detection in hematologic neoplasms (Bionano Genomics, September 10, 2026). As with DL40425, MRD and therapy-response testing are carved out of scope.
Renal Carcinoma Transcriptional Biomarkers: Proposed Non-Coverage
DL40429 takes the opposite direction. MolDX proposes that transcriptional and proteomic classifiers used for therapeutic decision-making in renal cell carcinoma are not currently supported by sufficient evidence for Medicare coverage. The draft sets out a prospective pathway rather than a blanket rejection: a test can qualify for future coverage if it demonstrates material improvement in risk prediction or therapy-response prediction beyond existing clinical-pathologic factors, achieves independent validation, and passes MolDX's technical assessment process. For labs with RCC transcriptional panels in the pipeline, this draft is effectively a checklist of the evidence CMS wants to see before it will reconsider.
What Labs, RCM Teams, and Ordering Clinicians Should Do Now
These are proposed LCDs, not final policy — they carry no binding coverage effect until finalized, and public comment periods are open. That said, the operational planning should start now. Molecular labs running hematologic panels should map their existing menu against the DL40425 decision-point criteria and the DA60490 exclusion list, since claims that fall outside "initial diagnosis, progression, or relapse" risk denial once the policy is final. Billing and RCM teams should note the DEX Z-Code and one-unit-of-service requirements, and flag the six-month re-testing review trigger in their claim-scrubbing logic. Ordering clinicians and genetic counselors documenting medical necessity should be explicit about which of the three covered decision points a test is addressing — that single sentence in the chart note is what will separate a clean claim from a suspended one. Labs building genome-wide CNA/SV workflows should track DL40407 closely, since it signals Medicare's growing comfort with single-workflow replacements for cytogenetic test bundles. Our related coverage on Medicare coverage for genetic testing and on reducing genetic testing denials covers how LCD language like this translates into day-to-day claim outcomes.
Frequently Asked Questions
Are DL40425, DL40407, and DL40429 final Medicare policy?
No. All three are proposed LCDs posted August 21, 2026, with public comment periods open. They carry no binding coverage effect until MolDX and the relevant MAC finalize them, which typically follows CMS's standard LCD comment and notice process.
Which Medicare contractors are affected?
All three drafts were posted in parallel by Palmetto GBA, CGS Administrators, and Noridian Healthcare Solutions — the three MolDX-participating MACs, whose combined jurisdictions cover most Medicare Part B billing nationally.
Does DL40425 cover minimal residual disease (MRD) testing?
No. MRD monitoring is explicitly excluded from DL40425, as is solid tumor testing, circulating tumor DNA testing, and germline testing. Coverage under this draft is limited to NGS panels at initial diagnosis, progression/transformation, or confirmed relapse.
What does "not covered" mean for the renal carcinoma biomarker LCD?
DL40429 proposes that current transcriptional and proteomic classifiers for renal cell carcinoma lack sufficient evidence for Medicare coverage. It also sets a forward path: independent validation and a MolDX technical assessment showing material improvement over existing clinical-pathologic data could support future coverage.
What should labs do while the comment period is open?
Review test menus against each LCD's clinical criteria and exclusions, update billing logic for the DEX Z-Code and six-month re-testing review trigger described in DA60490, and consider submitting comments to the relevant MAC before the policies finalize.
This article is provided for general educational and business-planning purposes for laboratory, revenue cycle, and clinical operations professionals. It is not legal, coding, billing, or medical advice, and coverage policy can change before or after finalization. Confirm current LCD status and specific claim requirements directly with the relevant Medicare Administrative Contractor before making billing or test-menu decisions.
Sources: CMS Medicare Coverage Database (DL40424/40450/40426, DL40406/40430/40410, DL40428/40432/40434, DA60490); Discoveries in Health Policy, "MolDx Issues Bonanza of New LCDs in Late August 2026" (Sept. 2026); Bionano Genomics press release, Sept. 10, 2026. See also our guides to Medicare coverage for genetic testing, genetic testing denials, and the ScreenMyGene homepage.