Intrahepatic cholangiocarcinomas are rare and risk factors remain incompletely understood, but one recently identified potential risk factor is chronic hepatitis C (HCV) infection. To further study this potential association, we searched for dysplasia in the intrahepatic bile ducts in native explanted livers in cases of chronic HCV and control groups. Cases of chronic biliary tract disease were excluded. A total of 1058 explants were reviewed: HCV (511), alcohol alone (112), HCV and alcohol (85), HBV (67), cirrhosis from other causes (149), and noncirrhotic livers, for example, cases transplanted for acute liver failure (134). Dysplasia of the intrahepatic bile ducts was seen in 19/1058 (1.8%) of cases and was associated with chronic HCV infection and alcohol use, P=0.01. Ten out of 19 cases of dysplasia were in the setting of chronic HCV, 5/19 were in the setting of alcohol alone, and the remaining 4/19 were in the setting of combined HCV and alcohol. Seventeen out of 19 cases were classified as low-grade dysplasia and 2/19 as high-grade dysplasia. In all cases of dysplasia, the lesions were multifocal and involved septal-sized bile ducts. In 16/19 cases, the dysplasia was papillary whereas in 3/19 cases the dysplasia was flat. In conclusion, dysplasia can be found within the intrahepatic bile ducts in chronic HCV cirrhosis, supporting recent epidemiologic studies identifying chronic HCV as a major risk factor for intrahepatic cholangiocarcinoma. Alcohol also seems to be a risk factor. The dysplastic changes are multifocal, involve septal sized bile ducts, and are typically papillary.