A poor prognosis of oral squamous cell carcinoma (SCC) is partly due to the invasiveness and metastasis of the tumor. A key element in tumor invasion and metastasis in the degradation of extracellular matrix is matrix metalloproteinases (MMPs). This study was performed to determine the expression of MMP-2 and MMP-9 of oral SCCs with regard to the histologic invasiveness and differentiation in 5 normal oral mucosa and 36 oral SCCs. The histologic invasiveness of oral SCCs were classified into 4 grades. The differentiation of oral SCCs was divided into 3 grades. The streptavidin-biotin immunohistochemical staining, using MMP-2 and MMP-9 monoclonal antibodies, was performed to determine the expression of MMP-2 and MMP-9. The expression of MMP-2 was positive in 6 of 17 oral SCCs with weak invasiveness and was positive in 7 of 19 oral SCCs with strong invasiveness. The MMP-2 expression did not increase significantly with respect to the invasiveness of oral SCCs (P>0.05). The expression of MMP-9 was strongly positive in 6 out of 17 SCCs with weak invasiveness and was strongly positive in 14 of 19 SCCs with strong invasiveness. The MMP-9 expression increased significantly with respect to the invasiveness of oral SCCs; the stronger the expression, the stronger the invasiveness (P<0.05). The expression of MMP-9 was in 57.9% of well differentiated SCCs, 57.1% of moderately differentiated ones, and 33.3% of poorly differentiated SCCs. The expression of MMP-2 and MMP-9 did not increase significantly with respect to the histologic differentiation. We conclude that with respect to the invasiveness, the MMP-9 expression increases significantly in oral SCCs but the MMP-2 expression does not; and that with respect to the histologic differentiation, their expressions do not increase significantly. These results suggeste that MMP-9 can be used as a tool to evaluate the invasiveness of oral SCCs.