Alteration in expression of E-cadherin and catenins is associated with loss of differentiation, acquisition of an invasive phenotype and poor clinical outcome in many types of cancer. To identify molecular prognostic markers, membrane expression levels of E-cadherin, and alpha-, beta- and gamma-catenin in biopsy samples (n=135) of oral squamous cell carcinoma (OSCC) were evaluated immunohistochemically in relation to preoperative tumour-related features, clinical course and prognostic value, and were found to be significantly correlated with an endophytic growth pattern and pathologically proved lymph-node metastasis. Alteration of expression of E-cadherin, and alpha-, beta- and gamma-catenin was also significantly correlated with poor disease-specific 5-year survival (P=0.0096, 0.0434, 0.0005 and 0.0005, respectively). Multivariate Cox proportional hazard regression analysis showed that alteration of beta- and gamma-catenin expression was a significantly independent prognostic parameter for survival (P=0.0112 and 0.0088, respectively), as was the case with endophytic growth pattern and advanced N-category. These results indicate that patients with OSCC and absent or reduced membrane expression of beta- and gamma-catenin should be considered a high-risk group for regional lymph-node metastasis and poor prognosis.