Cholangiocarcinoma (CC) arises from the biliary epithelium and in most cases represents adenocarcinoma. Pathomorphological evaluation is of decisive impact for the prognosis and management of CC. Morphological subtyping (histotype; hilar vs peripheral type), TNM classification, lymphatic spread, and resection margin status are of prognostic relevance. Distinction from hepatic metastases may be aided by immunohistology and clinico-pathological correlation. There is convincing evidence of the development of CC via premalignant lesions, especially biliary intraepithelial neoplasia, although further knowledge about the biology and diagnostic definition of these lesions has to be accumulated. Currently, there are no established molecular markers of prognosis or therapeutic target structures to be evaluated at the tissue level. Future progress is needed and expected in novel differential diagnostic and predictive markers, in uniform definition of resection margin status and further understanding of molecular and morphological changes in the development of CC.