familial melanoma appear on the chromosome arms 1p, 9p and 12q. Multiple genetic events have been related to melanoma's pathogenesis (disease development). The multiple tumor suppressor 1 (CDKN2A/MTS1) gene encodes p16INK4a – a low-molecular weight protein inhibitor of cyclin-dependent protein kinases (CDKs) – which has been localised to the p21 region of human chromosome 9. FAMMM is typically characterized by having 50 or more combined moles in addition to a family history of melanoma. It is transmitted autosomal dominantly and mostly associated with the CDKN2A mutations. People who have CDKN2A mutation associated FAMMM have a 38 fold increased risk of pancreatic cancer. Other mutations confer lower risk, but are more common in the population. People with mutations in the MC1R gene are two to four times more likely to develop melanoma than those with two wild-type (typical unaffected type) copies. MC1R mutations are very common, and all red-haired people have a mutated copy. Mutation of the MDM2 SNP309 gene is associated with increased risks for younger women. Fair- and red-haired people, persons with multiple atypical nevi or dysplastic nevi and persons born with giant congenital melanocytic nevi are at increased risk. A family history of melanoma greatly increases a person's risk, because mutations in several genes have been found in melanoma-prone families. People with a history of one melanoma are at increased risk of developing a second primary tumor. Fair skin is the result of having less melanin in the skin, which means less protection from UV radiation exists. A family history could indicate a genetic predisposition to melanoma. Pathophysiology The earliest stage of melanoma starts when melanocytes begin out-of-control growth. Melanocytes are found between the outer layer of the skin (the epidermis) and the next layer (the dermis). This early stage of the disease is called the radial growth phase, when the tumor is less than 1 mm thick, and spreads at the level of the basal epidermis. Because the cancer cells have not yet reached the blood vessels deeper in the skin, it is very unlikely that this early-stage melanoma will spread to other parts of the body. If the melanoma is detected at this stage, then it can usually be completely removed with surgery. When the tumor cells start to move in a different direction – vertically up into the epidermis and into the papillary dermis – cell behaviour changes dramatically. The next step in the evolution