This report was performed to study the biological role of c-Met in oral tumorigenesis by analyzing its expression in relation to clinicopathological features. Seventy-three cases of oral squamous cell carcinoma and 10 of normal mucosa were analysed for c-Met expression by immunohistochemistry. Normal oral squamous epithelium showed absent or low membranous positivity in the intermediate (malpighian-spinous) layer. Fifty-seven cases (78%) of carcinoma showed immunopositivity, with a prevalently membranous positivity and scattered areas also showing a cytoplasmic localization. Sixteen cases of carcinoma (22%) showed no positivity for c-Met. Among positive tumours, well-differentiated areas showed low or absent cytoplasmic positivity, while low-differentiated areas showed both membranous and cytoplasmic positivity. There was no statistically significant correlation between c-Met expression and sex, recurrence, staging or grading. The frequency of lymph node metastases was higher in c-Met-positive tumours (17/57, 29%) than in c-Met-negative ones (4/16, 25%). When analysed for prognostic significance, patients with negative/reduced c-Met expression had better survival rates than patients with high expression. The difference between survival rates was statistically significant (p<0.05). These data suggest that c-Met expression may be useful to identify cases of oral squamous cell carcinoma with a more aggressive and invasive phenotype.