The study of four cloverleaf skulls (two fetuses, one infant, and a young adult) concerns two Pfeiffer syndromes, a thanatophoric dysplasia and an isolated case. Clinical and radiologic examinations showed malformations at the level of the calvarium, the base, orbital cavities, and, sometimes, limb abnormalities. Correlations between these findings and the microradiographic analysis of nondemineralized sections elucidate this trilobular appearance of the skull. Premature temporoparietal suture closure terminates at a constricted surface of the lateral sides of the skull during the fetal life. Extension of the synostosis to coronal and frontal sutures and thickening of the occipital bone squama block lengthening of the skull. The consecutive reduction in skull volume is compensated by the maintenance of the permeability during the neonatal period of the sagittal and lambdoid sutures. Microradiographic examination shows that this anomaly may be of vascular origin and associated with abnormal osteoclastic resorption.