Interest in achieving this distinction increased in 2002 with the recognition of the oncogenic role of the BRAF V600E mutation in approximately 58–69% of papillary thyroid cancers (PTC) (15, 16). However, genetic testing for BRAF V600E alone for the detection of PTCs is inadequate for clinical decision making due to its low sensitivity of 60% for PTC (17). Indeed, our group first published its use in indeterminate and suspicious thyroid lesions and found it to add minimal clinical value (18). In addition to studying the diagnostic utility of BRAF V600E, numerous studies have investigated the association of BRAF V600E and patient prognosis. However, the correlation between BRAF V600E and clinical features of PTCs has yielded inconsistent results. Some studies report that BRAF V600E is associated with a more advanced phenotype including an increased risk of lymph node metastasis, cancer recurrence, and patient mortality (19–21), while others report no such associations (22). Moreover, thyroid cancer with BRAF V600E and TERT promoter mutations has been associated with worse clinico-pathological outcomes (23, 24). BRAF testing can also be useful in deciding treatment in the setting of known metastatic thyroid cancer. Direct tyrosine kinase inhibitors, such as vemurafenib (25), dabrafenib (26), and sorafenib (27), have been shown to be effective in BRAF V600E metastatic thyroid cancers.