A comparative study of Bowen's disease (BD) with or without chronic arsenic exposure may contribute to understanding arsenic carcinogenesis. We compared the p53 overexpression and proliferative activity of 26 cases of BD with chronic arsenic exposure (group I) and 22 comparable cases of BD without chronic arsenic exposure (group II) by immunohistochemical method on formalin-fixed, paraffin-embedded tissues with antibodies PAb1801 and MIB-1, respectively. We also included in this study two squamous cell carcinomas that developed from BD in group I and one in group II. Two paired BD lesions in the same individual of one patient in group I and of three patients in group II were also studied. The significant p53(+) (>10% stained cells) rates were 42.3% (11 of 26) and 9.1% (2 of 22) for groups I and II, respectively, and the difference was statistically significant (P = .01). The p53 expression in different lesions of the same individual remained consistently the same. Squamous cell carcinomas that developed in 2 cases of p53(+) BD in group I were also positive, but the one in 1 case of p53(-) BD in group II was negative. No significant statistical difference in proliferative activity was found between group I BD and group II BD (P= .769), nor between p53(+) cases (>10% stained cells) and p53(-) cases (<10% stained cells) in group I BD (P = .519). This study showed that significant overexpression of p53 protein was higher in BD with chronic arsenic exposure. Therefore, arsenic carcinogenesis of BD might be different from that of BD unrelated to arsenic, and alteration of p53 plays a more important role in the pathogenesis of BD with chronic arsenic exposure. Overexpression of p53 was not a prerequisite for developing squamous cell carcinoma and was not affected by proliferative activity.