In fluke-related CCA the most frequent mutation are represented by ACVR1B, ARID1A, FBXW7, MAP2K4, MSH3, SMAD4, BRCA1, H3K27me3-associated promoter mutations, PTEN and TP53 and also ERBB2 amplification with a major clinical implication due to the tumor’s response to ERBB2 inhibitor treatment. The gene discussed is ERBB2; the disease is neoplasm.