The lamprey is the only basal vertebrate in which large-scale gene perturbation analyses are feasible at present. Studies on this unique animal model promise to contribute both to the understanding of the basic neural-crest gene regulatory network architecture, and evolution of the neural crest. In this review, we summarize the currently known regulatory relationships underlying formation of the vertebrate neural crest, and discuss new ways of addressing the many remaining questions using lamprey as an experimental model.