Chronic cholestatic liver disease may be complicated by hepatobiliary malignancy. The early detection of hepatocellular carcinoma and cholangiocarcinoma is of paramount importance in the evaluation of candidates for liver transplantation, which remains the only effective treatment modality for advanced primary biliary cirrhosis and primary sclerosing cholangitis. This article reviews the identification of patients at high risk, current techniques for diagnosis, and makes recommendations for screening high-risk patients. This article also reviews preliminary data from the Mayo Clinic regarding liver transplantation for cholangiocarcinoma following radiation therapy.