Employing this approach, we identify a 43-gene embryonic melanoblast signature that predicts metastatic melanoma patient survival, and we introduce a role for KDELR3 that is distinct from KDELR1. A metastasis suppressor screen highlights KAI1/CD82 (hereafter referred to as KAI1) as a KDELR3-regulated protein. This evidence concerns the gene CD82 and metastatic melanoma.