BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with the development of cholangiocarcinoma in up to 10 % of patients. Cholangiography or endoscopic tissue sampling does not reliably distinguish between cholangiocarcinoma and a benign dominant bile duct stenosis. The aim of the present study was to assess the value of cholangioscopy for distinguishing between benign and malignant dominant stenoses in PSC patients. PATIENTS AND METHODS: Fifty-three PSC patients with dominant bile duct stenoses were prospectively studied. Transpapillary cholangioscopy and endoscopic tissue sampling were carried out in addition to endoscopic retrograde cholangiography (ERC). The cholangiography and cholangioscopic findings were classified as malignant or benign by the investigators. A final diagnosis of malignant stenosis was based on positive histology and/or cytology, whereas a benign condition was assumed in cases of negative tissue sampling and uneventful extended clinical follow-up. RESULTS: Twelve PSC patients (23 %) had dominant bile duct stenoses caused by cholangiocarcinoma, whereas 41 of the 53 patients (77 %) had benign dominant bile duct stenoses. Cholangioscopy was significantly superior to ERC for detecting malignancy in terms of its sensitivity (92 % vs. 66 %; P = 0.25), specificity (93 % vs. 51 %; P < 0.001), accuracy (93 % vs. 55 %; P < 0.001), positive predictive value (79 % vs. 29 %; P < 0.001), and negative predictive value (97 % vs. 84 %; P < 0.001). Transpapillary cholangioscopy is more sensitive and specific for characterizing malignant bile duct stenosis in comparison with endoscopic brush cytology. CONCLUSIONS: Transpapillary cholangioscopy significantly increases the ability to distinguish between malignant and benign dominant bile duct stenoses in patients with PSC.