The sphenoid bone represents a complex structure in terms of anatomy and embryology. Indeed, it is formed by the fusion of different primordia whose embryonic origins are different. In mammals, it is possible to distinguish two components of this bone: the orbitosphenoid and the basi-post-sphenoid derive from the cephalic mesoderm whereas the alisphenoid and the basi-pre-sphenoid are from neural crest cell origin. The genetic control of the development of these two components is different further increasing the heterogeneity of these components. The sphenoid bone has been linked with several developmental diseases: chordomas, tumors arising from notochordal remnants; persistence of the craniopharyngeal canal may result in the occurrence of trans-sphenoidal encephaloceles.