Song Y, Xu G, Ma T, et al. - Fine‐needle aspiration (FNA) is usually the standard preoperative tool for diagnosing thyroid nodules, however, some samples are classified as indeterminate, leading to unnecessary surgery, so researchers conducted this prospective, blinded cohort study to assess the value of next‐generation sequencing (NGS) for cancer diagnosis in indeterminate thyroid nodules. This investigation was performed on 189 patients, with 196 Bethesda III/IV nodules. Enough DNA and RNA were collected in 188 nodules, with 34.6% of them showing mutations or fusions. RAS, followed by BRAF V600E, were the most frequently mutated genes. Multigene testing showed sensitivity, specificity, positive predictive values (PPV), and negative predictive value (NPV) of 73%, 80%, 71%, and 82%, respectively. Furthermore, the PPV and NPV were 71% and 74% if four intermediate nodules were counted as malignant. The results allow more stratification of Bethesda III/IV thyroid nodules based on the risk of their malignancy. As benign markers, SPOP, EZH1, and ZNF148 mutations may be used.