Multiple primary melanoma (MPM) is a well-known phenomenon, but outcome studies regarding patients with MPM are rare. Aim of our study was to analyze whether MPM are less likely to metastasize than single primary melanomas (SPM). In our study disease progression (defined by the occurrence of regional lymph node or distant metastases) in cases of MPM was compared to cases of SPM on a sample of 1698 melanomas. Statistically significant difference in the occurrence of disease progression was found between the analyzed groups, progression being significantly less frequent in patients with MPM (P=0.009). Also, MPM occurred significantly more frequently in male patients (P= 0.001). We attribute these results not only to early detection of subsequent MPM, but to a variety of possible reasons, including different genetics and biology of tumors and, possibly, the immune response of the host. Further studies are required to elucidate these interesting findings.