Surgical specimens from 65 patients with squamous cell carcinoma (SCC) of the oral cavity were examined immunohistochemically. The clinicopathological significance of the expression of epidermal growth factor receptor (EGFR) and matrix metalloproteinase-3 (MMP-3) was assessed. Among the 65 tumours, 20(30.8%) and 37(56.9%) tested positively for EGFR and MMP-3, respectively. A positive correlation between the expression of EGFR and MMP-3 was found. The expression of EGFR in oral SCCs was associated with an advanced T stage of the primary tumour, an advanced pathological stage, and a high incidence of neck metastasis. In addition, MMP-3 was primarily expressed at the advancing front of cancer with a diffuse invasive mode. Thus, overexpression of MMP-3 was associated with an advanced pathological stage, a diffuse invasive mode, and a high incidence of neck metastasis. The analysis of MMP-3 expression is useful to evaluate the pathological status of tumours. Because EGFR-overexpressed tumour should produce larger amounts of MMP-3 in vivo, a close examination of oral SCC for expression of EGFR and MMP-3 should be helpful to predict their malignant potential.