Overexpression of p53 protein has been demonstrated in a variety of human malignant tumors, and its role in oncogenesis and tumor progression is thought to be important. Recently, some reports have suggested that p53 overexpression might be an indicator of immaturity or proliferative activity of cells in cutaneous lesions. The aim of the present study was to clarify the relationship between overexpression of p53 protein and the proliferative activity evaluated by Ki-67 immunostaining in well-differentiated squamous cell carcinoma (SCC) of the skin. Sixteen cases of well-differentiated SCC were analyzed by immunohistochemistry for the expression of p53 protein and Ki-67 antigen. p53 protein was detected in 12 out of the 16 cases (75%). The percentage of p53-protein-positive tumor cells (DO-7 index) ranged from 0 to 80.4 (mean +/- SD = 33.8 +/- 29.7) and the percentage of Ki-67-antigen-positive tumor cells (MIB-1 index) from 23.4 to 65.1 (mean +/- SD = 42.3 +/- 15.8). Cases with higher DO-7 indices tended to show higher MIB-1 indices and the correlation was statistically significant. Overexpression of the p53 protein seems to be a useful indicator of proliferative activity in cutaneous SCC.