Objective To explore the expression and the clinical significance of neural cadherin (N-cadherin) in perihilar cholangiocarcinoma. Methods The expression of N-cadherin was detected by immunohistochemical method in 26 patients with perihilar cholangiocarcinoma and 5 samples of normal bile duct tissues. The expression of N-cadherin was also compared by Western blotting assay between perihilar cholangiocarcinoma and paraneoplastic tissues. Results The im-munohistochemical results showed that positive expression of N-cadherin was observed in 14 of 26 patients with perihilar cholangiocarcinoma and in 6 of 26 paraneoplastic samples (53.84%vs 23.08%, P<0.05). There was 0 N-cadherin expres-sion in normal bile duct tissues. The positive rate of N-cadherin expression was higher in low differentiated group than that in middle and well differentiated groups. The result of Western blotting assay showed that N-cadherin expression was signifi-cantly higher in perihilar cholangiocarcinoma than that in the paraneoplastic tissues (0.88 ± 0.12 vs 0.43 ± 0.09, P < 0.05). Conclusion N-cadherin may be involved in the occurrence and development of perihilar cholangiocarcinoma.