BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). BRAF mutation frequencies are highly controversial in biliary tract cancers ranging from 0 to 33% for BRAF V600E. As most studies with high BRAF mutation rates were performed on European cohorts, this has raised the question of whether these discordant results represent a regional difference in the genetics of biliary tract cancer. In large cohort of biliary tract cancers including intrahepatic cholangiocarcinomas, extrahepatic cholangiocarcinomas, and adenocarcinomas of the gallbladder, BRAF V600E mutations were only rarely found in intrahepatic cholangiocarcinomas and were not identified in any cases of gallbladder adenocarcinoma. The clinicopathologic significance of BRAF V600E remains to be further elucidated in adenocarcinoma of the gallbladder. Various BRAF inhibitors (Vemurafenib, Dabrafenib) have been FDA approved for therapy for some tumor types in certain settings. These results should be interpreted in the clinical and radiographic context.