The "trephined" syndrome is a relatively rare complication after a large skull bone defect, consisting of a sunken skin above the bone defect with neurological symptoms such as severe headaches, mental changes, focal deficits, or seizures. Emerging data show improvements in the patients' neurological status after cranioplasty, i.e. the surgical intervention to repair cranial defects. Herein we report a 55-year-old man who attended our Neurorehabilitation Research Institute for a chronic disorder of consciousness (DOC) due to a severe right nucleo-capsular hemorrhage. His motor and neuropsychological status greatly improved after cranioplasty. Our results confirmed previous reports that cranioplasty may significantly improve neuropsychological and motor function, as evaluated by specific tests, in patients with skull bone defects, and even in patients with DOC.