Coloration of the skin, hair and eyes is controlled, in part, by MC1R. Polymorphisms in the MC1R gene determine the activity level of MC1R. Variants of the MC1R gene that lead to reduced MC1R function result in the production of predominantly the red/yellow pheomelanin pigment and fair skin that does not tan, and light eyes and hair. Fully functional MC1R stimulates production of the black/brown eumelanin.1 People harboring less functional variants of MC1R accumulate more mutations due to increased exposure of the nuclei to UV damage. If mutations accumulate in sensitive regions of the genome, then skin cancers can arise.Melanoma, a malignant tumor arising from melanocytes, is a rare disease, affecting only 22.1 out of 100,000 people in the US (Cancer statistics from the Center for Disease Control and Prevention). However, it is also a very deadly disease accounting for 75% of skin cancer deaths though it only accounts for 4% of skin cancer cases. In 2019, it is expected that 96,480 new cases of melanoma will be diagnosed, and 7,230 people will die in the US alone (American Cancer Society). This review will go over a brief history of melanoma, the major molecular defects that lead to melanoma progression, the major methods for diagnosing and determining patient prognosis and melanoma treatment options.