p53 is one of the most frequently mutated genes in human tumors including head and neck tumors like oral squamous cell carcinoma. It might be responsible for more than 50% of all relapses in patients with surgically treated oral carcinoma and clean margins. The aim of the present study was to explore p53 protein expression in peritumoral tissue and correlate it with relapse of the disease. The study included 25 patients (17 males and 8 females) with oral squamous cell carcinoma in the period August 2006 till August 2008. For immunohistochemical assay, a monoclonal antibody against p53 protein was applied (clone DO-7, DAKO Glostrup, Denmark). Peritumoral expression of p53 was as follows: 10 out of 25 cases (40%) were negative, 2 cases (8%) showed weak, 5 cases (20%) moderate and 8 cases (32%) strong p53 positivity. No significant correlation between peritumoral expression of p53 protein and patient’s relapse was found. In contrast, we found a trend toward association between intratumoral p53 expression and patient’s relapse (p=0.07). There was also trend toward higher peritumoral p53 expression in females comparing with p53 expression in males (52.9% of males did not have p53 expression while 87.5% females had mild, moderate or high p53 expression, p=0.088). Peritumoral expression of p53 protein is frequently seen in oral squamous cell carcinoma and merits further research.