We examined five cases of verrucous carcinoma (VC) and two cases of giant condyloma of Buschke-Löwenstein (GCBL) associated with invasive squamous cell carcinoma (ISCC), by immunocytochemistry and molecular techniques. Neither human papillomavirus (HPV) footprints nor p53-altered expression and/or mutation were observed among the cases of VC. By contrast, both cases of GCBL with ISCC turned out to be HPV 6 or 11 positive, showed overexpression of p53 and, one of the two, a mutation in the nucleotide sequence of this tumor suppressor gene. The results point out that VC and GCBL with ISCC, in spite of some morphologic similarities, are two distinct entities, the former being unrelated to both HPV and p53 inactivation and the latter related to both. Regarding p53, immunocytochemical and molecular data on GCBL with ISCC suggest a role of mutant p53 in the progression of malignancy into invasion.