The expression pattern of two Ca(2+)-dependent cell-cell adhesion molecules, E- and P-cadherin (CD), in 25 primary gingival squamous cell carcinomas (SCC) was examined immunohistochemically. The occurrence of reduced-type expression of both E- and P-CD increased significantly with the grade of carcinoma differentiation, culminating in a complete loss of P-CD in poorly differentiated SCC. The occurrence of reduced-type P-CD expression also increased significantly with the mode of invasion, as was the case with E-CD. Furthermore, no P-CD molecules were detected in one of the six SCC having a diffuse, cord-like invasion and in three of the six having a diffuse type of invasion. These findings suggest that the down-regulation of these cell adhesion molecules closely correlates with the differentiation grade and mode of invasion of gingival SCC.