Expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) helps to establish the origin of biliary and metastatic carcinomas. We investigated the expression of CK7 and CK20 in inflammatory, metaplastic and neoplastic conditions of the bile ducts, and evaluated possible relationships between the CK expression pattern and extrahepatic bile duct/gallbladder carcinomas (EBDCs) or intrahepatic bile duct carcinomas (IBDCs). We used immunohistochemistry for the investigation of 48 formalin-fixed, paraffin-embedded specimens grouped as: A) lithiasic or inflamed surgically resected extrahepatic bile ducts/gallbladders: all were CK7+/CK20+; B) percutaneous liver biopsies from patients with chronic hepatitis C primary biliary cirrhosis and primary sclerosing cholangitis: all were CK7+/CK20-; C) EBDCs: all were CK7+/CK20+, except for two cases which were CK7-/CK20-; D) IBDCs: all were CK7+/CK20-, except for one case showing CK20 positivity. Metaplastic changes were seen only among specimens in groups A and C: in these cases, CK20 was either focally or diffusely expressed. Our study suggests that the expression of cytokeratins under specific stimuli can be different from normal tissues, and that sometimes CK20 expression can be related to and precede the occurrence of metaplastic alterations.