Mutations in BRAF are commonly seen in thyroid carcinoma and can have therapeutic and prognostic implications. The BRAF V600E mutation is seen in approximately 40% of cases of papillary thyroid carcinoma (PTC), and is associated with aggressive clinicopathological features, higher recurrence rate, and disease related mortality. Significant advances have occurred in the development of new therapeutic targets of the MAP kinase pathway, which is activated in the setting of BRAF mutations, including BRAF and mitogen extracellular kinase (MEK) inhibitors. BRAF alterations other than V600E are less common in PTC, and their clinical significance remains to be established. Here we present a case of a male with poorly differentiated thyroid carcinoma, with papillary and follicular features, who was noted to have a BRAF K601E mutation. The patient was subsequently treated with a BRAF inhibitor, dabrafenib, and MEK inhibitor, trametinib.