The G-protein-coupled receptor, endothelin receptor B (EDNRB), is an important regulator of melanocyte survival and proliferation. It acts by stimulating downstream heterotrimeric G proteins, such as Gα and Gα . Constitutively active, oncogenic versions of Gα and Gα drive melanomagenesis, but the role of Ednrb in the context of these mutant G proteins has not been previously examined. In this paper, we used a knock-in mouse allele at the Rosa26 locus to force oncogenic GNAQ expression in melanocytes in combination with Ednrb gene knockout. The resulting pathological analysis revealed that every aspect of melanomagenesis driven by GNAQ was inhibited. We conclude that even in the presence of oncogenic Gα , the Ednrb receptor activates normal Gα and Gα proteins. This likely promotes tumorigenesis by activating phospholipase C-beta, the immediate effector of Gα . These findings suggest that it might be possible to target upstream receptors to offset the effects of hyperactive G proteins, recognized as the cause of a growing number of human disorders.