Acrocallosal syndrome (ACS) is an autosomal recessive disorder characterized by craniofacial dysmorphism, agenesis or hypoplasia of the corpus callosum, duplication of the phalanges of the hallux, more rarely the thumbs, post-axial polydactyly, syndactyly and severe mental retardation. Here we report the two first descriptions of acrocallosal syndrome in fetus with extensive neuropathological study and provide new data regarding additional brain abnormalities in ACS. The first case was a 25-gestational week male fetus displaying craniofacial and limb abnormalities, with bilateral syndactyly of the fourth and fifth fingers, preaxial polydactyly of the left foot and an inter-frontal extra-bone. The second fetus was a 33-gestational week male fetus. His left hand displayed a broad thumb and 4/5 syndactyly. In both cases, gross examination of the brain showed an absence of corpus callosum associated with interhemispheric cysts. The cerebral cortex in front of the cysts was nodular. Upon microscopic examination, the nodular masses corresponded to large dysplastic areas represented by clusters of undifferentiated neurons in the white matter. The cyst wall showed arachnoidal and ependymal covering and contained numerous choroid plexus, suggesting a developmental abnormality of the ventricles. The pons and the cerebellum were hypoplastic. The dentate nuclei were fragmented. Numerous neuronal heterotopias associated with ectopic ependymal cavities were observed in the vermis in one case. The olivary nuclei were severely dysplastic too. We hope that these new data will make both the ante- and post-natal diagnosis easier, facilitate comparisons with animal models and encourage the identification of the genes responsible for this syndrome.