Both types of functional psychosis schizophrenia and manic depressive illness (MDI) share several epidemiological, clinical and genetic characteristics. Subtle morphological changes as evidenced by neuroimaging techniques have also been reported in both entities. Thus far, neuropathological changes have been described in schizophrenia only. We report four cases of MDI with neuropathological changes similar to those found in schizophrenia, i.e. definite disturbances in the cytoarchitecture within the entorhinal region indicating a migrational malformation in the superficial layers possibly originating in the second fetal trimester. A limited sector of the rostro-ventral insula showed a diminution of the nerve cell population. We suggest a vulnerability factor secondary to fetal developmental impairment in the entorhinal region common to both schizophrenia and MDI.