A poor prognosis of oral squamous cell carcinoma (SCC) is partly due to the invasiveness and metastasis of the tumor. One of key elements in tumor invasion and metastasis in the degradation of extracellular matrix is tissue inhibitors of metalloproteinases (TIMPs). This study was performed to determine the expression of TIMP-1 and TIMP-2 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 process, using TIMP-1 and TIMP-2 monoclonal antibodies, was performed to determine the expression of TIMP-1 and TIMP-2. The expression of TIMP-1 was positive in 5 of 17 oral SCCs with weak invasiveness and was positive in 8 of 19 oral SCCs with strong invasiveness. The TIMP-1 expression did not increase significantly with respect to the invasiveness of oral SCCs (P>0.05). The expression of TIMP-2 was strongly positive in 5 out of 17 SCCs with weak invasiveness and was strongly positive in 15 of 19 SCCs with strong invasiveness. The TIMP-2 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 TIMP-1 and TIMP-2 did not increase significantly with respect to the histologic differentiation. We concluded that with respect to the invasiveness, the TIMP-2 expression increases significantly in oral SCCs but the TIMP-1 expression does not; and that with respect to the histologic differentiation, their expressions do not increase significantly. These results suggested that TIMP-2 can be used as a tool to evaluate the invasiveness of oral SCCs.