Cancers arise because of the accumulation of mutations in critical genes that alter normal programs of cell proliferation, differentiation, and death. The RAS-RAF-MEK-ERK-MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in approximately 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. ARAF and c-RAF are infrequently mutated in human cancer. However, BRAF is mutated in a wide range of human cancers. Most mutations are within the kinase domain, with a single amino acid substitution (V600E) accounting for most mutations.