Cholangiocarcinomas occasionally arise in the nonbiliary cirrhotic liver, but their pathobiologic features remain unsettled. To characterize such cholangiocarcinomas, we examined immunohistochemically the expression of MUC3, MUC5AC, MUC6, and MUC7 apomucins in hepatic tissue specimens from 4 patients with cholangiocarcinoma and viral cirrhosis, 24 patients with cholangiocarcinoma without cirrhosis, and 16 patients with combined hepatocellular-cholangiocellular carcinoma. The cholangiocarcinomas associated with cirrhosis and the cholangiocarcinoma elements of combined hepatocellular-cholangiocellular carcinoma rarely expressed MUC3 and MUC5AC, but the cholangiocarcinomas not associated with cirrhosis frequently expressed these apomucins. MUC6 apomucin was widely expressed in cholangiocarcinomas, irrespective of the association with cirrhosis and also in the cholangiocarcinoma elements of the combined hepatocellular-cholangiocellular carcinomas. MUC7 apomucin was expressed frequently in cholangiocarcinomas associated with cirrhosis and combined hepatocellular-cholangiocellular carcinomas and infrequently in cholangiocarcinomas without cirrhosis, particularly those arising at the hepatic hilus. The similarity of the apomucin profiles between cholangiocarcinomas associated with cirrhosis and the cholangiocarcinoma elements of combined hepatocellular-cholangiocellular carcinoma suggests a similar or common histogenesis and that cholangiocarcinoma associated with cirrhosis might be derived from the combined type.