In the last decade, an extensive molecular characterization demonstrated that the mutations in KRAS, SMAD4, ARID1A, GNAS, and IDH1/2 gens as well as FGFR2 fusions have been associated mostly with CCA, whereas EGFR, ERBB3, and PTEN mutations are prevalent in GBC. This evidence concerns the gene SMAD4 and cholangiocarcinoma.