BACKGROUND: The abnormal expression of atypical protein kinase C-ι(aPKC-ι) subtype and E-cadherin play important roles in tumor occurrence and progression. This study was designed to investigate the correlation of expression of aPKC-ι and E-cadherin with the clinicopathological characteristics and prognosis of cholangiocarcinoma, and to analyze the molecular mechanisms of invasion and metastasis of the tumor. METHODS: EnVision immunohistochemistry was used to detect the expression of aPKC-ι and E-cadherin in 9 specimens of benign bile duct tissues, 35 specimens of cholangiocarcinoma and 6 specimens of metastatic cholangiocarcinoma. The relationship of the expression with clinicopathological characteristics, invasion and prognosis of cholangiocarcinoma was analyzed. A multivariate regression analysis was made of these data by the Cox proportional hazard model. RESULTS: The positive expression level of aPKC-ι in cholangiocarcinoma was remarkably higher than that in benign bile duct tissues (68.6% vs. 11.1%, P=0.006), but the expression level of E-cadherin was lower in cholangiocarcinoma than in benign bile duct tissues (37.1%vs. 88.9%, P=0.016). Correlation analysis revealed that the expression of aPKC-ι was positively related to tumor differentiation and invasion, whereas that of E-cadherin was entirely the contrary. Moreover, there wasa negative relationship between the expression of aPKC-ιand that of E-cadherin (r=-0.287, P