One case of median cleft lip with hypotelorism and two cases of cyclopia, all with brains exhibiting alobar holoprosencephaly, were examined by detailed anatomical dissection. The results indicate that the variations of the skull and associated soft structures form a continuum, as do the brain, eye, and face, from the mild to severe end of the syndrome. At the mild end, the bony malformations were primarily limited to the structures derived from the frontonasal prominence, within which the ethmoid bone was the focal point. Malformed soft structures included the muscles of the anterior and posterior neck regions. At the severe end of the spectrum, these structures were more severely malformed, and the sphere of malformations widened to include more peripherally located bones and soft structures such as the mandible, ear ossicles, muscles of mastication, and salivary glands. Possible mechanisms for the generation of the malformations are addressed.