Cutaneous pigmentation is a major determinant of the cutaneous response to ultraviolet radiation, and consequently of the risk of developing skin cancer. Over the past 10 years, several genes involved in melanogenesis have been identified, including the melanocortin 1 receptor gene. Recent work on the melanocortin 1 receptor suggests that it is a key player in determining whether eumelanin or pheomelanin is predominantly produced both in vitro and in vivo. In the mouse, variants of this receptor, which differ in their ability to activate adenylyl cyclase, are associated with different coat colors. In humans, melanocortin 1 receptor variants are associated with red hair and fair skin, and work in progress from our laboratory suggests that certain melanocortin 1 receptor variants may preferentially be associated with hair color rather than skin type. In addition, melanocortin 1 receptor variants are a risk factor, possibly independent of skin type, for melanoma susceptibility.