Integrins are cell adhesion molecules that mediate the cell to extracellular matrix interactions. We sought to determine whether the integrin expression on tumor cells is associated with invasive and metastatic potential. First, in 8 cell lines of oral squamous cell carcinoma, 4 of which were metastatic in nude mice and 4 of which were not, integrin expression was examined. When these cell lines were cultured in vitro or transplanted into the tongues of nude mice, the metastatic cell lines tended to show a stronger expression of alpha 2, alpha 3, alpha 5, and alpha 6 integrins than did the nonmetastatic cell lines. Second, integrin expression was immunohistochemically examined in 65 biopsy specimens of primary oral squamous cell carcinoma. In invasive or metastatic cases, a marked expression of alpha 2, alpha 3, alpha 5, and alpha 6 integrins was frequently observed. The association of integrin expression with the mode of tumor invasion and nodal involvement was found to be statistically significant. These results suggest that integrin expression is closely associated with tumor invasion and nodal involvement in oral squamous cell carcinoma.