Expression of abnormal p53 protein is a widely recognised marker of malignancy including oral squamous cell carcinoma. This is a longitudinal study of p53 expression in fixed, paraffin-embedded tissue from 3 patients with multiple, recurrent, squamous cell carcinomas of floor of mouth (n = 4, 4, 3). All carcinomas demonstrated increased expression of p53 compared to normal tissues. However, there was reduction in expression from primaries to subsequent recurrent tumours in all 3 patients. The significance of reduction of expression of p53 in sequential recurrences is unclear, but as each of these patients has now survived for at least 5 years this may be a phenomenon indicating a favourable prognosis. As this study relates to only 3 patients, a larger study is needed to confirm this initial observation.