To support the clinical findings on the genetic duet of BRAF V600E and TERT promoter mutations and demonstrate its biological relevance, we used in vitro and in vivo models to examine the roles of BRAF V600E and TERT in oncogenic cellular activities and xenograft tumor development of PTC cells BCPAP and K1 and melanoma cells A375, which all harbored both BRAF V600E and TERT promoter mutations. The gene discussed is BRAF; the disease is melanoma.