Prolonged nitric oxide (NO) production by the enzyme type II nitric oxide synthase (NOS2) has been implicated in angiogenesis and metastasis of human cancers. In animal models, wild-type p53 (but not mutant) protein results in down-regulation of NOS2 expression, which reduces both tumour growth and dissemination. In the current study, we aimed to find out whether a correlation was present in oral squamous cell carcinoma. Fifty-six cases of squamous cell carcinoma were assessed immunohistochemically using antibodies to NOS2 and p53 (clone DO-7). We also confirmed NOS2 protein expression in selected cases using immunoblotting. The results were correlated with clinicopathological findings. Statistical analysis showed a significant relationship between p53 and NOS2 expression (P= 0.001). No relationship was found between size of tumour or histological degree of differentiation, and NOS2 expression in the primary tumour.