1. The major identified risk factor for the development of cholangiocarcinoma in Western countries is primary sclerosing cholangitis (PSC). 2. The diagnosis of cholangiocarcinoma in PSC requires a high index of suspicion because endoscopic brush cytology and/or biopsies and imaging studies are often negative for malignancy. Positron emission tomography is a promising imaging modality for the diagnosis of cholangiocarcinoma, even in patients with PSC. 3. A serum carbohydrate antigen 19-9 value greater than 100 U/mL has a sensitivity and specificity for cholangiocarcinoma of approximately 75% and 80%, respectively. 4. Liver transplantation is a viable therapeutic option for selected patients with early-stage cholangiocarcinoma. Outcomes are optimized by using preoperative radiation and chemotherapy and ensuring the absence of metastases by an exploratory laparotomy.