It is worth remembering the ERβ agonist diarylpropionitrile (DPN) efficacy in inhibiting NRAS (Neuroblastoma RAS Viral Oncogene Homolog)-mutated melanoma cell proliferation [24], as well as many specific ERβ agonists of natural origin able to exert an antitumor function in different human melanoma cell lines in vitro and in vivo [61]. This evidence concerns the gene ESR2 and melanoma.