Because IDH1 and 2 are not the only genes involved in the IDH pathway, the analysis of IDH1/2 mutations will miss the identification of ICC cases that are not mutated at IDH1/2 but are disturbed by alterations in other genes involved in the IDH pathway and disposed to hypermethylation at a specific set of the genes. This evidence concerns the gene IDH2 and intrahepatic cholangiocarcinoma.