Glutamate signaling has been shown to have a role in melanoma progression, in part through activating mutations in the metabotropic glutamate receptor 3 (GRM3) gene. We hypothesize that altered glutamate signaling affects the development and function of melanocytes, endowing these cells with properties important for melanoma progression. By expressing mutant GRM3 variants in developing zebrafish melanocytes, we determined how oncogenic GRM3 variants affected these cells. In embryonic melanocytes oncogenic GRM3 mutants disrupted trafficking of melanosomes, causing their aggregation in the cell body. Wild-type GRM3 had no effect on melanosome distribution. Melanosomes are trafficked in a cAMP-dependent manner, and drugs that directly or indirectly increase cAMP levels were able to rescue the melanosome phenotype of oncogenic GRM3-expressing melanocytes. Our data indicate that oncogenic GRM3 variants dysregulate cyclic AMP (cAMP) signaling, a heretofore unknown role for these oncogenes. Preliminary data in cultured melanoma cells indicate that oncogenic GRM3 leads to a reduction of cAMP levels as compared to wild-type GRM3 or EGFP. cAMP signaling has been implicated in melanoma progression and drug resistance, and our data show that oncogenic properties of GRM3 could be mediated, at least in part, by alterations in cAMP signaling.