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UCLA Health - Molecular Testing of Thyroid Nodules

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Author: UCLA Health
Categories: Health
Tags: health
Views: 2 · Last viewed: 2026-10-16 15:00 UTC

Short Summary

Main recommendation: If a thyroid nodule's fine needle aspiration biopsy comes back indeterminate (Bethesda 3 or 4), molecular testing on the nodule can help decide whether surgery is needed. A benign molecular result lowers the cancer risk to about 4 to 5 percent, often allowing surgery to be avoided, while a suspicious result raises it to about 50 percent and typically leads to removing half the thyroid.

Key Points

  • Thyroid nodules are very common: nearly half of people in a neck ultrasound screening would have one, and most are benign.
  • The workup starts with a neck ultrasound, which scores how suspicious a nodule looks, followed by a fine needle aspiration (FNA) biopsy for more suspicious nodules.
  • The Bethesda System grades biopsy results: Bethesda 2 is benign, Bethesda 5 or 6 is likely cancerous, and Bethesda 3 or 4 is indeterminate, with roughly 20 percent cancer risk.
  • Molecular testing is only useful for indeterminate biopsy results, since benign and malignant biopsy results already settle the question.

Details Worth Noting

  • Concrete instructions: Get a neck ultrasound first. If suspicion is very low, return after a set interval and repeat the ultrasound to confirm the nodule is not changing. If more suspicious, get an FNA biopsy. If the biopsy is indeterminate (Bethesda 3 or 4), order molecular testing on the same needle-collected material, which is covered by most insurance. If the molecular test is benign, avoid surgery and watch with a yearly ultrasound to check for growth. If suspicious, plan a diagnostic lobectomy (removal of the half of the thyroid containing the nodule) for a definitive diagnosis.
  • UCLA uses two tests the speakers consider the most well studied: Afirma GSC (Gene Sequencing Classifier), which relies on RNA, and ThyroSeq v3, which relies on DNA and RNA. The speakers say both performed well in their own patients.
  • Without molecular testing, operating on everyone with an indeterminate biopsy means about four of five patients would have surgery for a benign nodule.
  • A suspicious molecular result does not confirm cancer; it indicates a roughly 50 percent likelihood, which is why surgery is still used to confirm the diagnosis.
  • The speakers direct viewers to the UCLA website for more information and an appointment phone number.

Bottom Line

Molecular testing is most valuable for the roughly one-third of biopsies that come back indeterminate, because a benign result can spare patients unnecessary surgery.