Epidermolysis bullosa simplex (EBS) is a heritable skin disorder characterized by skin fragility and blistering. While its most severe variant, dystrophic epidermolysis bullosa (DEB) is associated with squamous cell carcinoma (SCC), the development of extracutaneous neoplasms in EBS is extremely rare. We report a novel case of supratentorial primitive neuroectodermal tumor (sPNET) in a 7-year male with EBS. Experience of radiation therapy and its challenges in children with EBS has rarely been reported. Pediatr Blood Cancer 2010; 54:170–172. © 2009 Wiley-Liss, Inc.