Cholangiocarcinoma is a primary malignancy of biliary epithelium. Risk factors for cholangiocarcinoma include primary sclerosing cholangitis and other conditions that produce chronic inflammation of the biliary tree. The diagnosis of cholangiocarcinoma can be elusive; it is often not made until advanced disease is present and at a stage when a curative surgical resection is not feasible. Currently used diagnostic modalities include serum and bile tumor markers, radiologic and endoscopic imaging, and pathologic analysis. Surveillance strategies to increase the chance of early diagnosis should be strongly considered in individuals at high risk for cholangiocarcinoma. Patients with long-standing primary sclerosing cholangitis would be the ideal candidates for a screening program.