Molecular and Proteomic Diagnostic Testing for Hematology and Oncology Indications - (0520) — MM 0520 | CIGNA Coverage Update

TL;DR: Cigna Healthcare modified MM 0520, its molecular and proteomic diagnostic testing coverage policy for hematology and oncology, effective November 4, 2025. Here's what billing teams need to know before submitting claims.

Cigna Healthcare updated Coverage Policy MM 0520 governing molecular and proteomic diagnostic testing across hematology and oncology indications. This modification affects over 110 CPT codes — spanning BCR/ABL1 analysis (81206, 81207, 81208), FLT3 mutation testing (81245, 81246), JAK2 variants (81270, 81279, 0017U, 0027U), EGFR analysis (81235), KRAS testing (81275, 81276), and a substantial list of codes Cigna now considers experimental or investigational. If your practice bills somatic mutation testing, tumor profiling, or hematologic gene panels for Cigna patients, this coverage policy change is live and affects your reimbursement now.

Quick-Reference Table

Cigna Molecular and Proteomic Diagnostic Testing Coverage Criteria and Medical Necessity Requirements 2025

The Cigna molecular and proteomic diagnostic testing coverage policy under MM 0520 addresses somatic — not germline — mutations. These are acquired or post-conception changes in tumor or blood cell DNA. The policy covers testing that informs disease staging, recurrence risk, or treatment selection for specific cancers and blood disorders.

Medical necessity under this policy is code-specific and indication-specific. Cigna does not issue a blanket approval for molecular oncology testing. Each CPT code has its own criteria, and billing without meeting those criteria is a direct path to claim denial.

The policy covers tests like JAK2 V617F analysis (81270) for myeloproliferative disorders, BCR/ABL1 quantitative testing (81206, 81207, 81208) for chronic myelogenous leukemia, FLT3 internal tandem duplication and tyrosine kinase domain analysis (81245, 81246) for acute myeloid leukemia, and IDH1/IDH2 variant testing (81120, 81121) for glioma. These are medically necessary when the patient meets the applicable selection criteria in the policy — and not before.

Prior authorization requirements are not explicitly spelled out in the summary language for every individual code, but molecular diagnostic testing at this complexity level regularly triggers prior auth review under Cigna. Verify prior authorization requirements for each code through Cigna's online portal before submitting. Don't assume coverage equals no prior auth.

DPYD testing (81232) for 5-fluorouracil and capecitabine drug metabolism and TYMS analysis (81346) are also covered under the applicable criteria. So is MGMT promoter methylation analysis (81287) for glioblastoma — a code that gets denied frequently when ordered without documented glioblastoma diagnosis. MSI analysis (81301) for Lynch syndrome and hereditary non-polyposis colorectal cancer is covered when criteria are met.

Reimbursement for these codes depends entirely on documentation. The diagnosis must support the specific test ordered. Ordering a FLT3 panel for a lymphoma patient instead of an AML patient, for example, will fail medical necessity review.

Cigna Molecular Diagnostic Testing Exclusions and Non-Covered Indications

Cigna explicitly designates 13 codes as experimental, investigational, or unproven under MM 0520. These are hard exclusions — not borderline cases. Billing them for Cigna patients will result in claim denial, full stop.

The experimental/investigational list includes several prostate cancer molecular tests. Cigna does not cover the Oncotype DX Genomic Prostate Score (0011M), exosome-based sncRNA panels (0343U, 0424U, 0433U), AI-assisted whole-slide imaging analysis for prostate cancer risk stratification (0512U, 0513U), or mRNA gene expression profiling for prostate cancer (0497U, 0498U). If your urology or pathology team has been ordering these, they need to know Cigna is not paying for them under this policy.

Pan-tumor epigenetic testing (0332U), whole-exome somatic paired tumor/normal analysis (0036U), tumor methylation marker NGS (0486U), plasma proteomics for lung cancer prediction (0436U), and pancreatic cancer algorithmic gene analysis (0510U) are also classified as experimental. These are codes where the clinical community may see utility, but Cigna has not accepted the evidence base. Billing them is a coverage policy violation, not a gray area.

The real financial risk here is inadvertent billing of these experimental codes. Labs and pathology groups sometimes bill the most specific or most recently released code available. If your charge capture or lab billing system defaults to one of the 0-series PLA codes above, you need to catch that before the claim goes out.

Coverage Indications at a Glance

Cigna Molecular Oncology Billing Guidelines and Action Items 2025

CPT, HCPCS, and ICD-10 Codes for Molecular and Proteomic Oncology Testing Under MM 0520

Covered CPT Codes (When Medical Necessity Selection Criteria Are Met)

Note: The policy data references 31 additional covered CPT codes beyond those listed above. Pull the full MM 0520 policy document from Cigna's provider portal for the complete covered code list.

Not Covered / Experimental CPT and PLA Codes

Key ICD-10-CM Diagnosis Codes

The MM 0520 policy data does not include specific ICD-10-CM codes in the source document. Cigna's medical necessity criteria reference clinical indications (AML, CML, glioma, NSCLC, CLL, myeloproliferative disorders, etc.) rather than specific ICD-10 codes. Use the most specific ICD-10 diagnosis code that matches the documented clinical indication for each test ordered. Your coding team should map each molecular test to the appropriate confirmed or suspected malignancy code — not a screening or family history code — to support medical necessity.