Ultraviolet radiation (UV) from sunlight is a known carcinogen for skin cancers and skin is the largest human organ in direct contact with sunlight’s UV. Majority of carcinogenic mutations induced by UV are the UV-signature, cytosine to thymine transitions, generated from the DNA adducts called Cyclobutane Pyrimidine Dimers (CPDs) [1-3]. Skin has specialized cells called melanocytes that produce melanin, a pigment known to be a potent shield against UV exposure. Contradicting the photoprotective properties of melanin, we discovered that melanin itself is oxidized by combinatorial activity of Nitric Oxide Synthase (NOS) and NADPH Oxidase (NOX). This oxidation produces Reactive Carbonyl Species (RCS) in excited triplet state that generate CPDs in complete absence of UV. The role of this pathway, which we named “melanin chemiexcitation” [4] remains under-represented in melanoma which is one of the deadliest of all skin cancer types.