Patients with SD-type ICC usually have a history of chronic liver disease, and their tumors commonly harbor mutations in IDH1, BAP1 and FGFR2, whereas patients with LD-type cancer have a history of premalignant biliary intraepithelial neoplasia, and their tumors most commonly show genetic changes in SMAD4 and KRAS7,9,11. Here, SMAD4 is linked to intrahepatic cholangiocarcinoma.