In this issue of JAMA Otolaryngology Head & Neck Surgery, Valderrabano et al1 report provocative findings on the performance of a widely used molecular test for thyroid nodules. The authors’ goal was to determine whether the performance of this assay, the Afirma gene expression classifier (GEC; Veracyte), in the real world has matched the figures in the initial validation study that led to the approval and widespread adoption of the GEC. Undertaking a systematic review of 19 studies encompassing 2568 nodules, the authors found that the sensitivity and specificity of the test seemed to differ markedly from those reported in the initial study.2