Morphogenesis of craniopharyngeal derivatives of the neurohypophysis found in 14 Fischer 344 (F344) rats was studied. The incidence of the craniopharyngeal derivatives was 0.17% in male (7 out of 4,200) and 0.16% in female (7 out of 4,450) F344 rats. Neither a sex-related difference in their incidence nor a strain-related difference in their morphological features was observed. Craniopharyngeal derivatives were composed of aberrant epithelial structures consisting of serous acinar and tubular and fusiform cell structures, and most of these derivatives were associated with Rathke's cleft cysts, which are suggestive of a congenital background. The acinar structures were positive for periodic acid-Schiff reaction and negative for Alcian blue stain. Immunohistochemically, cells forming these structures were positive for cytokeratin, and basal cells of the acinar or tubular structures and some of the fusiform cells showed positive staining for alpha-smooth muscle actin. Electron microscopically, these spindle-shaped basal cells had intracytoplasmic myofilaments with focal density in their cytoplasm, and they were regarded to be myoepithelial cells. These findings strongly indicate that the craniopharyngeal derivatives are not a neoplastic lesion but rather are a developmental aberration derived from the stomatodeum, which is known to be the origin of both nasal and oral epithelial tissues, including the parotid glands, other than Rathke's pouch.