A functional single nucleotide polymorphism (SNP) 309 T/G within mouse double minute 2 (MDM2) gene has been linked to onset and outcome of disease in tumors. Two published studies have shown discordant results regarding the effect of this SNP on age at diagnosis of cutaneous melanoma (CM) in Caucasian female populations. Here, we examined the age at diagnosis and clinical associations of CM with SNP309 and the related polymorphism, p53 Arg72Pro, in an Italian population (249 CM patients and 291 cancer-free controls) composed of women and men. MDM2 intronic region of 294 bp was directly sequenced, whereas Arg72Pro SNP was analyzed by polymerase chain reaction-restriction fragment length polymorphism. No associations were found among the SNP309, Arg72Pro, risk of CM, age at diagnosis and presence of metastasis in total subjects and when stratified according to the gender. The SNP309 was significantly associated with tumor Breslow thickness. The P-value in the minor allele recessive mode was 0.02, and the odds ratio (OR) adjusted for gender and age was 3.11 (95% confidential interval (CI)=1.21-8.00). The SNP309 is not associated with the risk and age of onset of CM, and the presence of metastasis in an Italian population but the SNP309 GG may be a risk genotype for increasing in tumor Breslow thickness.