The product of HPV E6 and E7 genes is able to inactivate both the p53 and pRb proteins. The aim of this study was to evaluate the correlation among anal HPV infection and nuclear p53 overexpression. The Authors evaluated HPV DNA by PCR and p53 nuclear expression by immunohistochemistry in 12 cloacogenic and 6 squamocellular carcinoma. HPV DNA was detected in 71.4% of the squamocellular tumors and in 57.1% of the cloacogenic tumors. In squamocellular tumors HPV types 31-33 and 16 were found; in cloacogenic tumors type 16 alone was detected. Nuclear accumulation of p53 was found to be associated with the presence of HPV. There was no significant difference in parietal infiltration, lymph nodes involvement and prognosis between HPV+p53+ patients and HPV-p53- patients. Tumor aggressiveness is likely to be enhanced by factors other than HPV infection and p53 overexpression.