Perineural invasion is associated with tumor spreading and an unfavorable prognosis in a variety of cancers. Recently, neural cell adhesion molecule (NCAM) has been reported to be affinitive to neural tissues, which suggests some relationship between NCAM and perineural invasion. This study was designed to elucidate the role of the expression of NCAM on the development of perineural invasion in bile duct cancer. A histopathologic study was performed on 24 patients with bile duct carcinoma who underwent resections. The overall incidence of NCAM expression in the resected specimen was 66.7% and that of perineural invasion was 87.5%. Furthermore, NCAM expression was shown to be positive in 16 (76%) out of 21 cases in whom perineural invasion was observed. A significant positive correlation was found between the expression of NCAM and perineural invasion in bile duct cancer. These results highlight an important role of NCAM in the development of perineural invasion in bile duct cancer.