Vertebrate brains are highly organized structures that show remarkable diversity throughout animal groups. The agnathans, which diverged from the gnathostomes early in the evolution of the vertebrates, occupy a key phylogenetic position from which to clarify the origin and evolution of the brain. We studied the developing lamprey brain and compared its developmental plan with that of the gnathostomes, in order to reconstruct the evolutionary processes of the vertebrate brain. We found that the lamprey brain has the basic molecular mechanisms necessary to form neuromeric compartments, and that its mesencephalon and diencephalon exhibit conserved morphological and molecular features. Conversely, the telencephalon and metencephalon display lamprey-specific developmental mechanisms. Thus, the molecular program of the nervous system is thought to have improved in the gnathostome lineage. Changes in the expression domains of some regulatory genes might have facilitated the evolution of the vertebrate central nervous system.