The epidermal nevus syndrome (ENS) is an unusual neurocutaneous disorder consisting of the combination of an epidermal nevus and a central nervous system (CNS), ophthalmological, and/or skeletal abnormality. The study reports four new patients with ENS. Each had a confirmatory biopsy of the epidermal nevus, abnormal neurological examination findings, and documented CNS anatomical studies by imaging or autopsy. The paper also reviews the literature in English to determine neurological abnormalities found in skin-biopsy-proven cases of ENS. Hemi-atrophy, hemimegalencephaly, migrational abnormalities and vascular anomalies were found to be the most frequent intracranial abnormalities associated with ENS. Seizures and/or disabling moderate to severe developmental delays were present in a majority of patients. Seizure onset during the neonatal period or early infancy was associated with major hemispheric malformations. Neuroectodermal-derived ocular lesions were often bilateral. No consistent relation between laterality of the nevus and laterality of CNS abnormalities was found, supporting the gene mosaicism theory of pathogenesis.