RET Proto-Oncogene Testing — CPB 0319 | AETNA Coverage Update

TL;DR: Aetna, a CVS Health company, modified CPB 0319 governing RET proto-oncogene germline testing, effective September 26, 2025. CPT codes 81404, 81405, 81406, and 88271 are covered when specific high-risk criteria are met — but HCPCS code S3840 is not covered for the indications listed in this policy.

Aetna's RET proto-oncogene coverage policy under CPB 0319 draws a hard line between covered germline testing and non-covered testing. If your team bills molecular pathology for MTC workups or hereditary endocrine tumor syndromes, this update directly affects how you document medical necessity and which codes you submit. Here's what the revised criteria require.

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Quick-Reference Table

Field	Detail Copy
Payer	Aetna, a CVS Health company
Policy	RET Proto-Oncogene Testing
Policy Code	CPB 0319
Change Type	Modified
Effective Date	September 26, 2025
Impact Level	Medium — specific hereditary endocrine and oncology practices
Specialties Affected	Endocrinology, Medical Genetics, Oncology, Molecular Pathology, General Surgery
Key Action	Verify that claims for CPT 81404, 81405, 81406, and 88271 include documentation linking the member to one of the three high-risk criteria groups before submitting

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Aetna RET Proto-Oncogene Coverage Criteria and Medical Necessity Requirements 2025

CPB 0319 Aetna defines two broad scenarios where germline RET testing meets medical necessity. Get either of these right on your claims and you're in good shape. Get them wrong and you're looking at a claim denial.

Scenario 1: High-risk family history or clinical presentation. Aetna covers germline RET mutation testing when the member meets any one of three criteria groups.

The first group is family history of medullary thyroid carcinoma (MTC). If a member has a first-degree blood relative — parent, full sibling, or child — with MTC, testing is covered. The testing strategy here is full sequencing of the RET gene.

The second group is a known familial RET mutation in a first- or second-degree relative. First-degree means parent, full sibling, or child. Second-degree means aunt, uncle, grandparent, grandchild, niece, nephew, or half-sibling. When a relative already has a confirmed germline RET mutation, Aetna expects the testing strategy to target that specific familial mutation — not a full sequencing panel.

The third group is personal clinical findings. The member doesn't need a family history flag if they personally have any of the following:

For this third group, full RET gene sequencing may be covered. These are the cases where your documentation needs to show the specific diagnosis driving the test order.

Scenario 2: Apparently sporadic MTC. Aetna also covers diagnostic germline RET testing for members with apparently sporadic medullary thyroid carcinoma. This matters because up to 25% of apparently sporadic MTC cases carry a germline RET mutation. Aetna's coverage policy recognizes that distinction.

The Aetna RET testing coverage policy does not mention prior authorization requirements explicitly within CPB 0319. That doesn't mean your plan contracts don't require prior auth — check your specific Aetna plan contracts for prior authorization requirements before assuming you can bill without it. Reimbursement for CPT 81404, 81405, and 81406 hinges on meeting these selection criteria, so your documentation has to carry the load.

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Aetna RET Proto-Oncogene Testing Exclusions and Non-Covered Indications

HCPCS code S3840 — "DNA analysis for germline mutations of the RET proto-oncogene for susceptibility to multiple endocrine" conditions — is explicitly listed as not covered for the indications in CPB 0319.

This is a meaningful distinction. S3840 describes functionally similar testing to the covered CPT codes, but Aetna has placed it in the non-covered group. If your lab or ordering provider historically used S3840 for RET testing claims, stop. That code will not pay under this policy.

The real issue here is code selection at the molecular pathology level. CPT codes 81404, 81405, and 81406 map to different tiers of molecular pathology complexity. The right code depends on the specific mutation analysis performed. Using S3840 instead of the appropriate molecular pathology CPT is a billing error that creates a denial — and one that's hard to appeal because the payer has explicitly listed S3840 as non-covered.

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Coverage Indications at a Glance

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Aetna RET Proto-Oncogene Testing Billing Guidelines and Action Items 2025

The effective date of September 26, 2025 is already here. If you haven't audited your RET testing claims workflow, do it now.

Copy Action Items

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CPT, HCPCS, and ICD-10 Codes for RET Proto-Oncogene Testing Under CPB 0319

Covered CPT Codes (When Selection Criteria Are Met)

Not Covered Codes

Code	Type	Description	Reason Copy
S3840	HCPCS	DNA analysis for germline mutations of the RET proto-oncogene for susceptibility to multiple endocrine conditions	Not covered for indications listed in CPB 0319

Key ICD-10-CM Diagnosis Codes

The ICD-10 codes listed in CPB 0319 include a large range of non-small cell lung cancer codes (C34.x series). This is notable — RET fusions are a known driver in NSCLC, and this code list likely reflects the broader molecular testing context in which CPB 0319 operates. However, the covered criteria in this policy are specific to germline RET mutations tied to MTC and hereditary endocrine syndromes, not somatic RET fusion testing for lung cancer. The presence of C34.x codes in the policy does not mean germline RET testing for NSCLC meets the covered criteria above. If you bill RET testing for lung cancer indications, this policy does not govern that — and you should verify which Aetna policy applies.

The ICD-10 codes explicitly listed in the policy data are:

The policy data notes 20 additional C34.x ICD-10-CM codes not shown above. Review the full CPB 0319 policy at app.payerpolicy.org for the complete list.

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A note on the ICD-10 list: the disconnect between the C34.x lung cancer codes and the MTC/hereditary endocrine criteria in this policy is confusing — and you're right to be confused. The C34 codes likely reflect the broader context of RET testing across multiple policies or a code list that wasn't fully scoped to this policy's indications. Don't use lung cancer ICD-10 codes to support RET germline testing claims under the hereditary MTC criteria. If you're unsure how your documentation lines up with this code list, loop in your compliance officer before submitting.

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