OBJECTIVE The understanding of histopathological prognostic factors is critical to improving surgical outcome. This study investigated the microscopic features of cancer of the extrahepatic bile duct in order to clarify the prognostic determinants affecting surgical outcome. METHODS In 90 cancers of the extrahepatic bile duct, the correlation between several microscopic parameters and survival was investigated. Lymphatic, venous, and perineural invasion, and the surgical margin (tumor-free or tumor-positive) were examined with serial step-wise sectioned specimens. RESULTS Seven pT1-tumors showed no venous or perineural invasion and no lymph node involvement and were associated with prolonged survival (5 year survival, 86%) compared with pT2,3 tumors (23%). In pT2,3 tumors, lymphatic, venous, and perineural invasion was found in 80%, 47%, and 88%, respectively, with no significant differences in occurrence of these parameters according to the origin of the primary tumor. As for survival with pT2,3 tumors, lymph node involvement (58%) and status of the surgical margin were significant parameters (p=.0330 and p=.0309, respectively). In addition, these latter parameters differed significantly according to the origin of the primary tumor. CONCLUSIONS In cancer of the extrahepatic bile duct, lymph node involvement and status of the surgical margin were the most important microscopic parameters affecting prognosis.