Obesity is now a major health problem due to its rapidly increasing incidence worldwide and severe consequences. Among many conditions associated with obesity are some cancers including melanoma. Both genetic defects and environmental risk factors are involved in the carcinogenesis of melanoma. Activation of multiple signal pathways such as the PI3K/Akt and MAPK pathways are necessary for the initiation of melanoma. Activation of the MAPK pathway as a result of activating mutations in BRAF is commonly seen in melanoma though it alone is not sufficient to cause malignant transformation of melanocytes. Obesity can result in the activation of many signal pathways including PI3K/Akt, MAPK, and STAT3. The activation of these pathways may have a synergistic effect with the genetic defects thereby increasing the incidence of melanoma. J. Cell. Biochem. 114: 1955–1961, 2013. © 2013 Wiley Periodicals, Inc.