We studied p53 overexpression in a series of 99 primary oesophageal squamous cell carcinomas (28 well-differentiated, 42 moderately-differentiated and 29 poorly-differentiated squamous cell carcinomas) from Chinese patients using the p53 protein specific mouse monoclonal antibody DO-7 on paraffin sections. The p53 protein was detected in 30% (30 cases) of the tumours. A significantly higher positive rate was noted in the poorly-differentiated tumours (11% for the well-differentiated, 31% for the moderately-differentiated and 48% for the poorly-differentiated tumours). In addition, strong positive p53 staining was identified only in the less differentiated tumour cells in the periphery of the tumour cell nests in all the cases and the expression was weaker in the better differentiated foci. The central keratinizing areas and the immediately adjacent tumour cells were always negative for p53. The adjacent normal oesophageal mucosa was all negative for p53 protein but the non-invasive dysplastic epithelium next to the tumours could also be strongly positive for p53 protein (four out of 14 cases in which the dysplastic epithelium adjacent to the tumour was adequately sampled). In two out of these four cases, the dysplastic epithelium showed staining for p53; even the adjacent invasive tumour was negative for p53. It is concluded that there is a strong relationship between p53 overexpression and tumour cell differentiation in oesophageal squamous carcinoma and overexpression of p53 can occur in non-invasive tumour cells.