E-cadherin (E-cad) is a subclass of the cadherin family that plays a major role in maintenance of intercellular junctions in epithelial tissues. In order to explore the correlation between the expression of E-cad and cancer invasion and metastasis in vivo, we performed an immunohistochemical examination for E-cad expression in 120 patients with breast cancer using our specific anti-E-cad monoclonal antibody. In noncancerous epithelial cells, E-cad was strongly expressed on cell-cell boundaries, whereas various staining patterns were observed in tumors. Of these 120 tumors, 56 (47%) showed Pr type expression of E-cad, and 64 (53%) showed Rd type or negative expression. We found significant correlations between E-cad expression and clinicopathological features. The frequency of Rd type was significantly higher in invasive ductal carcinomas (58%, 56 of 97) and poorly differentiated carcinomas (84%, 21 of 25) than in noninvasive and well-differentiated carcinomas. Furthermore, a high frequency of Rd type was detected in the following advanced tumors: T3,4 tumors, 71% (22 of 31); tumors with extensive lymph node metastasis, 74% (29 of 39); and tumors with distant metastasis, 86% (19 of 22). These values were significantly higher compared with their counterparts. The expression of epidermal growth factor receptor tended to be positive in E-cad-positive tumors. However, no significant relationship was seen among E-cad expression, menopausal status, hormone receptor status, and DNA ploidy pattern. These results suggest that the reduction of E-cad expression may play an important role in invasion and metastasis of human breast cancer.