The 2015 American Thyroid Association (ATA) (60) and the 2016 American Association of Clinical Endocrinologists (AACE) (9) clinical guidelines recommend “considering,” molecular testing for indeterminate nodules. If molecular testing is being considered, ATA recommends that patients “should be counseled regarding the potential benefits and limitations of testing and about the possible uncertainties in the therapeutic and long-term clinical implications of results” (strong recommendation, low-quality evidence) (60). However, long-term outcome data on the use of molecular markers for therapeutic decision-making is currently unavailable. A recent report estimated that standard application of the GEC for all indeterminate thyroid nodules would result in only a 7.2% decrease in thyroidectomy volume (61). Similarly, two studies by our group showed that molecular markers did not significantly affect the surgical decision-making process, where only 7.9–8.4% of patients had altered clinical management as a result of molecular testing (39, 62). For these reasons, patient benefit from molecular marker use in routine clinical practice is likely marginal. Moreover, the AACE 2016 guidelines recommend molecular testing to complement cytologic evaluation in indeterminate nodules (Grade A recommendation), but only when the “results are expected to influence clinical management” (Grade A recommendation) (9). Testing for detection of BRAF, RET/PTC, PAX8/PPRG, and RAS mutations can be considered (Grade B recommendation). Furthermore, with the exception of BRAF V600E, there is insufficient evidence “to recommend in favor of or against the use of mutation testing as a guide to determine the extent of surgery” (Grade A recommendation) (9).