Basal cell carcinoma (BCC) generally has an indolent course but a subgroup of BCCs tends to grow aggressively into deep tissues and even metastasize. Although studies have shown a positive correlation between mutations in the tumor suppressor gene p53 and aggressive behavior in epithelial tumors, the results for BCC are conflicting. We aimed to determine whether there is any relationship between p53 expression in BCC and histopathologic subtype of the tumor.Thirty-three formalin-fixed BCC tissue samples were examined at Hazrat-e Rasool University Hospital, Tehran, Iran, from March 2003 to April 2004. Tumors were categorized as aggressive (infiltrative or morpheic) and non-aggressive (nodular or superficial) based on histopathological examination of hematoxylin and eosin sections. p53 expression was demonstrated by immunohistochemical staining using the monoclonal anti-p53 antibody (PAb240) and results were reported using a semiquantitative score. Expression of p53 was compared between aggressive and non-aggressive tumors. All of the 11 aggressive tumors exhibited nuclear staining in more than 50% of the tumor cells. In the 22 non-aggressive tumors, less than 50% of cells showed positive staining. p53 immunoreactivity was significantly higher in aggressive BCCs than non-aggressive ones (x(2) test; p < 0.01). No correlation was found between p53 expression and the age of the patient or site of the tumor. History of childhood radiotherapy correlated positively with higher levels of p53 expression. We conclude that expression of p53 might be used as a marker to predict the aggressiveness of BCCs.