Papillary thyroid carcinoma (PTC) is the most common histotype among the thyroid cancer types. Although PTC is a curable malignancy, many patients relapse after treatment. Thus, there is a need to identify novel factors involved in the pathogenesis of PTC that may be used as targets for new therapies. The MAPK pathway has been implicated in the pathogenesis of PTC. Therefore, in this review, we summarize the role of the BRAF V600E mutation in the development and progression of thyroid cancer. The cinical implication of this molecular abnormality is also discussed. It is evident that the detection of the BRAF V600E mutation is crucial in order to identify novel avenues for thyroid cancer treatment.