Objective: To synthesize evidence on the clinical value, cost-effectiveness, and practical indications of molecular testing in thyroid nodules, focusing on Bethesda III-IV cytology.
Methods: Structured narrative review. PubMed was the primary source, while Google Scholar was used only as a supplementary tool for citation tracking and selected health-economic studies. Searches covered database inception to December 2025.
Results: BRAF(V600E) has high specificity and is mainly useful for rule-in purposes, whereas its sensitivity is limited. Multigene next-generation sequencing panels, notably ThyroSeq v3, provide both rule-out and partial rule-in support. Expression/genomic classifiers such as Afirma are more helpful for reducing unnecessary surgery in low-to-intermediate baseline risk settings, especially in Bethesda III nodules. In Bethesda IV nodules, testing more often refines risk and surgical planning than replaces diagnostic surgery. Diagnostic yield and cost-effectiveness vary according to baseline malignancy prevalence, test price, surgical costs, and payer model. Robust Vietnamese economic data are lacking.
Conclusion: Molecular testing is an adjunct rather than a replacement for clinical assessment, ultrasound, and FNA, and should be used only when results are likely to alter management.