Primary sclerosing cholangitis (PSC) is a significant risk factor for developing cholangiocarcinoma. Tests currently used to screen patients with PSC include serum tumor markers, invasive biliary imaging and sampling techniques, and noninvasive biliary imaging. The most commonly used serum markers are carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA). Invasive biliary imaging includes endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). In addition to standard cytology, the bile can be tested for CA 19-9 levels, as well as other novel tumor markers. In addition, the brushed cells can be analyzed for chromosomal abnormalities using digital image analysis (DIA) or fluorescence in situ hybridization (FISH). Nonivasive imaging techniques include computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), and positron emission tomography (PET).