A common polymorphism at codon 72 of exon 4 encoding either arginine or proline has been shown to confer a susceptibility to the development of skin tumor in renal transplant recipients. Moreover, this polymorphism may affect proteolytic degradation of p53 promoted by E6 protein from mucosal human papillomaviruses and represent a risk factor for human-papillomavirus-induced carcinogenesis. In this study, we analyzed the human papillomavirus presence and the TP53 allele distribution in cutaneous squamous cell carcinoma of renal transplant recipients and immunocompetent patients. Fifty-three squamous cell carcinomas from 40 renal transplant recipients, 50 benign epithelial skin lesions from 50 renal transplant recipients with no history of skin cancer, 51 squamous cell carcinomas from immunocompetent patients, and 29 blood samples from immunocompetent individuals without skin cancer were investigated. Human papillomavirus DNA was detected using polymerase chain reaction performed with two pairs of primers (MY09-MY11 and FAP59-FAP64). TP53 allele distribution was studied by denaturing gradient gel electrophoresis assay, followed by sequencing analysis. Human papillomavirus DNA was detected in 64% of squamous cell carcinoma and 79% of benign epithelial lesions from renal transplant recipients (NS) and only in 37% of squamous cell carcinoma from immunocompetent patients (p < 0.05). Mucosal oncogenic human papillomavirus types were predominant in squamous cell carcinoma from both renal transplant recipients and immunocompetent patients. Rate of arginine homozygosity in squamous cell carcinoma from renal transplant recipients was significantly higher (83%) than in immunocompetent patients with or without squamous cell carcinoma (60% and 59%, respectively). Our results suggest that TP53 arginine/arginine genotype could represent a potential risk factor for the development of squamous cell carcinoma in renal transplant recipients compared to immunocompetent patients. No association between TP53 arginine/arginine genotype and human papillomavirus status could be determined, however.