Malignant tumors are complex and therapeutic intervention often ineffective. To bring more structure in the complex nature of tumors, the hallmarks of cancer framework was developed. This conceptual framework encompasses ten cellular functions that make normal cells malignant cancer cells. These hallmarks are: genomic instability and mutation, tumor promoting inflammation, sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, deregulating cellular energetics and finally avoiding immune destruction. These hallmarks are functional within the context of the tumor microenvironment. The hallmarks of cancer form a general framework which can be applied to interpret alterations that occur in different types of cancer. Therefore it should predict that any specific type of can- cer shows oncogenic alterations that match the hallmarks described by Hanahan and Weinberg. The type of cancer selected to test this hypothesis is melanoma. This form of skin cancer represents only 4% of human skin cancers but is responsible for 75-80% of skin cancer deaths.