This study examined the relationship between immunohistochemically detectable p53 protein and prognostic factors in squamous cell carcinoma of the head and neck (SCCHN). Twenty-seven tumor specimens were evaluated utilizing a panel of three monoclonal antibodies (MAbs) directed against different epitopes of the p53 protein (PAb 421, PAb 1801, and PAb 240). The overall incidence of p53 protein detection with a panel of MAbs was 78%, which was significantly higher than with any one of the tested antibodies. Comparison of the tumors that were negative for p53 with tumors that stained positive with one or multiple antibodies, however, revealed no statistically significant differences with respect to the stage of disease, metastatic node involvement, size of the primary tumor, or degree of tumor differentiation. The results of our study suggest that levels of p53 protein, although commonly immunohistochemically detected in head and neck tumors, do not correlate with known prognostic factors for SCCHN.