The myriad of biological and environmental factors that are suspected to interfere in melanoma development leaves a wide-open window for hypotheses, and recent studies investigate estrogen-mediated signaling in melanoma (an impairment of estrogen signaling triggers cancer initiation, promotion and progression) [9], by assessing the role of ERα gene promoter methylation or the expression of G protein-coupled ER [10]. This evidence concerns the gene ESR1 and cancer.