BACKGROUND: Cholangiocarcinoma (CCa) is a recognised complication of primary sclerosing cholangitis (PSC) with prevalence rates of 8-18% reported from tertiary referral centres where screening protocols have lead to early identification of tumours. The aims of this study were to report the prevalence and outcome of CCa in PSC for a United Kingdom centre with a defined referral population. METHODS: All patients referred to the unit over a 20 year period from 1985-2004 with a diagnosis of PSC were prospectively entered into a departmental database. The database was interrogated to determine all patients who had in addition a diagnosis of CCa either at presentation or subsequently. For this cohort, the mode of presentation, management and outcome were determined. RESULTS: 370 patients (265 M and 105 F) with a median age of 50.5 years were referred with confirmed or suspected PSC of which 207 were subsequently transplanted. 48 patients (13%) developed a CCa with a mean interval from referral to tumour diagnosis of 4 months. The mode of presentation included: inoperable tumours at presentation (n=14); incidental findings in transplant hepatectomy specimens (n=13); PSC follow-up (n=9), transplant work-up (n=5), whilst on transplant waiting list (n=5), suspected tumour confirmed at transplant (n=1); and incidental finding at cholecystectomy. (n=1). The diagnosis was confirmed by: radiology-guided biopsy (n=27); MRI (n=2); CT (n=2); at laparoscopy/laparotomy (n=2); and by frozen section at transplant in 1 case. Management consisted of: transplantation (n=13, incidental on post transplant histology); hepatic resection (n=8); palliation through stenting (n=26); no treatment (n=1). The overall median survival was 5.3 months increasing to 7.6 months for transplant recipients and 52.8 months for patients undergoing resection. Survival for the palliation group was 2.8 months. CONCLUSIONS: CCa is a common finding in PSC. Unfortunately, many patients with CCa/PSC will have inoperable tumours by the time they are referred and regular screening of PSC patients at referring centres is advocated to detect early tumours as resection offers significantly better outcomes for this cohort of patients.