The brain is comprised of a remarkable cell-type diversity, which arises during embryonic and fetal development from neural stem cells and provides the basis for proper brain function. Production errors in the tightly orchestrated process of brain development can result in neurodevelopmental malformations. Alterations in the mTOR pathway result in a spectrum of defects ranging from focal cortical dysplasia to hemimegalencephaly (HME). HME is a rare disorder, characterized by the enlargement of one hemisphere. To date, a detailed cellular and molecular understanding of the neuropathological underpinnings of HME is missing. We have thus assessed the genetic, radiologic and histologic features of a fetal case of PTEN-associated HME (gestational week 22) to provide a comprehensive characterization of the cellular alterations in this malformation. Our results confirm many typical HME features like cortical dyslamination, an enlarged cortical plate, balloon cells and polymicrogyria. Stainings with specific neuron markers reveal that upper layer neurons are not correctly positioned within the cortical plate. Additionally, we have observed nodular heterotopias located in the outer subventricular zone of the megalencephalic hemisphere, which mainly consist of SATB2+cells that are usually found in the upper cortical layers. The megalencephalic hemisphere also exhibits significant alterations in the position and an increased number of TBR2+ and HOPX+ progenitor cells as compared to the unaffected hemisphere. These analyses and findings will provide a new standard for future characterization of neurodevelopmental malformations of the human fetal brain and thereby contribute to a deeper understanding of the pathomechanisms that drive altered brain development.