The vertebrate cranium is generally classified into the neurocranium and the viscerocranium. The latter is derived from the neural crest and so is the prechordal portion of the neurocranium. A view we favor considers the prechordal neurocranium as the premandibular component of the viscerocranium, and the vertebrate skull to consist of the neural crest-derived viscerocranium and the mesodermal neurocranium. Of these developmental units, only the viscerocranium appears to have completely segmented metamerical organization. The Hox code which is known to function in specification of the viscerocranium does not extend rostrally into the mandibular and premandibular segments. By genetic manipulation of rostrally expressed non-Hox homeobox genes, the patterning mechanism of the head is now demonstrated to be more complicated than isomorphic registration of the Hox code to pharyngeal arches. The phenotype by haplo-insufficiency of Otx2 gene, in particular, implies the premandibular cranium shares a common specification mechanism with the mandibular arch. Our interpretation of the metamerical plan of the viscerocranium offers a new scheme of molecular codes associated with the vertebrate head evolution.