The study reports frequent somatic mutations in the GNAQ gene, specifically at codon 209, in blue nevi (83%) and uveal melanoma (46%). These mutations result in constitutive activation of GNAQ, turning it into a dominant acting oncogene. The findings suggest an alternative pathway to MAP-kinase activation in melanocytic neoplasia, providing new therapeutic opportunities. The study also highlights the connection between nevus of Ota and uveal melanoma, as *GNAQ* mutations are identified as a genetic link between these conditions. Further experiments demonstrate that GNAQ^Q209L transforms human melanocytes and induces anchorage-independent growth, similar to other oncogenes like BRAF and NRAS. Additionally, GNAQ^Q209L transfection in uveal melanoma cells activates the MAP-kinase pathway, leading to increased phospho-ERK levels. Knockdown of GNAQ in uveal melanoma cells results in reduced cell growth, apoptosis, and changes in the cell cycle. These findings identify GNAQ as a novel oncogene in human neoplasia and suggest potential therapeutic targets for uveal melanoma, a highly aggressive cancer with limited treatment options.The study reports frequent somatic mutations in the GNAQ gene, specifically at codon 209, in blue nevi (83%) and uveal melanoma (46%). These mutations result in constitutive activation of GNAQ, turning it into a dominant acting oncogene. The findings suggest an alternative pathway to MAP-kinase activation in melanocytic neoplasia, providing new therapeutic opportunities. The study also highlights the connection between nevus of Ota and uveal melanoma, as *GNAQ* mutations are identified as a genetic link between these conditions. Further experiments demonstrate that GNAQ^Q209L transforms human melanocytes and induces anchorage-independent growth, similar to other oncogenes like BRAF and NRAS. Additionally, GNAQ^Q209L transfection in uveal melanoma cells activates the MAP-kinase pathway, leading to increased phospho-ERK levels. Knockdown of GNAQ in uveal melanoma cells results in reduced cell growth, apoptosis, and changes in the cell cycle. These findings identify GNAQ as a novel oncogene in human neoplasia and suggest potential therapeutic targets for uveal melanoma, a highly aggressive cancer with limited treatment options.