Oral squamous cell carcinoma is a challenging oncology problem. A reliable biomarker for metastasis or high-risk prognosis in oral cancer patients remains undefined. Using quantitative immunohistochemistry, we examined the expression of vimentin, E-cadherin, and beta-catenin in 83 oral squamous cell carcinoma patients, and the relationships between the expression of these markers and specific clinicopathological features were analysed. The high expression of vimentin was observed in 23 of 43 (53%) tumours from patients who eventually developed a recurrent tumour and was associated with recurrence and death (P<0.001 and <0.001, respectively). The decreased expression of E-cadherin was observed in 36 of 43 (84%) tumours from patients who eventually developed a recurrent tumour and was also associated with recurrence and death (P<0.001 and <0.001, respectively). Although no correlation between beta-catenin expression in whole-tumour sections and clinicopathological features was observed, decreased beta-catenin expression at the tumour invasive front was closely associated with recurrence and death (P=0.002 and 0.002, respectively). The expression of vimentin and that of E-cadherin were associated with survival and were independent prognostic factors in univariate and multivariate analyses. Our data show that the overexpression of vimentin was closely associated with recurrence and death in oral squamous cell carcinoma patients. The combination of the upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complexes at the tumour invasive front may provide a useful prognostic marker in oral squamous cell carcinoma.