The incidence of cutaneous melanoma has increased worldwide in the last 20 years. Research on potential risk factors, both environmental and genetic, has led us to some new and interesting conclusions. Ultraviolet radiation is clearly the main environmental risk factor for melanoma, but its relationship is complex and controversial. With regard to genetic factors, the discovery of two types of genes was a great advance in further understanding the biology of the melanocyte. CDKN2A (p16) is the prototype of the high-penetrance, low-prevalence gene related to melanoma. This gene has been studied in some families in which several members have been diagnosed with melanoma. In the general population with non-familial melanoma, low-penetrance, high-prevalence genes such as MC1R seem to be more interesting. Studies on the MC1R gene have not only shown its importance in skin and hair pigmentation, but also in the development of melanoma. Functional studies on CDKN2A and MC1R have led us to new and important conclusions. The analysis of data from studies on families, twins and control cases, with the collaboration of several countries, will lead us to new discoveries. For the primary and secondary prevention of this tumor, we must promote public health campaigns on the dangers of sun exposure and the identification of individuals at high risk.