A case of sudden cardiac death in a 3-year-old young male affected by Prader-Willi syndrome, clinically diagnosed and confirmed by means of DNA methylation, is presented. The infant suddenly collapsed at home and was taken apparently unconsciousness by his mother to the emergency clinic where he was pronounced dead. A complete postmortem examination was performed and the histological findings led to the definition of cardiac death with a typical picture of contraction band necrosis. Pulmonary hypoxic alterations are frequently reported as the primary cause of death in PWS cases. In this fatal case according to the macroscopic and microscopic findings, the cause of death was most likely cardiac and possibly related to contraction band necrosis linked with ventricular fibrillation and sudden death.