Cyclooxygenase-2 (COX-2) is known as one of the critical prognostic factors in carcinomas of the various organs. However, the importance of COX-2 overexpression in oral squamous cell carcinomas has not been fully described yet. We investigated overexpression of COX-2 by immunohistochemistry in 72 surgical specimens from patients with squamous cell carcinoma of the oral cavity, and evaluated correlations between COX-2 overexpression and clinicopathologic variables. The immunoreactivity of COX-2 was cytoplasmic. COX-2 overexpression was observed in 10 (13.9%) of 72 tumours and it was well correlated with lymph node involvement at the time of surgical treatment (P=0.011) and postoperative recurrence (P=0.025), but not with the other clinicopathologic variables including age, gender, tumour stage and histological grade. In addition, COX-2 overexpression showed a close association with postoperatively disease-free survival (P=0.039) and overall survival as well (P=0.043), and multivariate analyses revealed that COX-2 overexpression was an independent predictor for disease-free survival but not for overall survival. The current study suggests that overexpression of COX-2 could impact on disease-free survival for patients with oral squamous cell carcinoma and that selective inhibition of COX-2 is a possible target for the therapeutic strategies.