Cyclooxygenase-2 (COX-2) expression is up-regulated in transformed cells and in malignant tissues, including tumours of the head and neck, and it has prognostic significance in many types of cancer. COX-2 expression is suppressed by the wild-type but not by the mutant tumour suppressor gene TP53. The purpose of this study was to investigate the association between the expression of COX-2 and the clinical outcome in patients with oral and pharyngeal squamous cell carcinoma (SCC), and to examine its relationship to p53. Immunohistochemistry showed an elevated COX-2 expression in 88% (n = 57; strong 38, weak 19) of the 65 tumour samples. The staining intensity was not associated with patient or tumour characteristics, nor with the immuhistochemical expression of p53. Kaplan-Meier analysis showed no significant correlation between COX-2 expression and recurrence-free or overall survival, but a strong p53 expression was associated with a poor recurrence-free (p = 0.001, log-rank) and overall survival (p = 0.003). We conclude that, unlike strong p53 expression, COX-2 expression does not have prognostic significance in advanced oral and pharyngeal SCCs.