In the present study, we found that seven most recurrent mutations (TP53, KRAS, SMAD4, IDH1/2, FGFR2-fus and BAP1) showed pair-wise co-occurrences or mutual exclusivities in ICC, and could aggregate into three genomic clusters with distinct clinicopathological and molecular features, biological behaviors and therapeutic vulnerabilities. Here, IDH1 is linked to intrahepatic cholangiocarcinoma.