Among human cancers, melanoma remains one of the malignancies with an ever-growing incidence in white populations. Recent advances in biological and immunological therapeutic approaches as well as increased efforts for secondary prevention are contributing to improve the survival rates. It is likely that a significant fall in mortality rates for melanoma will be achieved by further increase of the early detection through a more accurate selection of the higher-risk individuals (i.e., carriers of predisposing genetic alterations). A similar scenario occurs in Italy. In the present review, we have considered data on incidence, survival and mortality rates of melanoma in Italian population, including evaluation of the main risk factors and genetic mutations underlying disease susceptibility.