Objectives: The aim of this study was to investigate the potential use of E-cadherin, a tumour-suppressor gene product involved in establishing cell-cell adhesion and one of its associated proteins, beta-catenin, as markers of nodal metastasis in oral squamous cell carcinoma (OSCC). Materials and Methods: Thirty invasive OSCCs in patients with (n = 19) and without (n = 11) nodal meta-stases, as confirmed on histopathologic examination of the resected regional lymph nodes (n = 30), were examined for E-cadherin and P-catenin expression by immunohistochemistry. Results: There was a highly significant association (P < 0.0001) between E-cadherin and beta-catenin expression and tumour differentiation by conventional Broders' grading of the whole tumour. Irrespective of the nodal status and invasive tumour front (ITF) grading score, however, loss of expression was recorded at the ITF in 28 (93%) of 30 tumours and 22 (73%) of 30 tumours stained for E-cadherin and beta-catenin respectively. Conclusion: The results of this study suggest an association between loss of expression of E-cadherin and beta-catenin and a lower degree of differentiation; however, their use as markers of nodal metastasis in OSCC appears unreliable.