This article presents a case report of a cranioplasty performed after a post-craniotomy empyema with osteitis. The skull reconstruction was performed using a bioceramic implant and a combined muscular free flap of latissimus dorsi and serratus anterior. This procedure not only provided coverage of a wide skull defect but also allowed the filling of the intracranial dead space. Clinically, we observed an improvement of the patient's preoperative neurological status with a near-complete correction of her right hemiparaesis and phasic disorders. Eight months after the cranioplasty, (1) no recurrence of infection was noticed; (2) no distortion of the skull was noticeable and (3) the patient again experienced a normal social life. Using computed tomography (CT) scan images, we observed a re-expansion of the left cerebral hemisphere without any dead space or extradural collection. The only observable sequelae were a temporoparietal alopecia (10 cm x 4 cm) and a winging of the scapula, induced by the skin graft and the removal of the lower-third of the serratus anterior muscle, respectively. The use of a muscular free flap associated with a customised biomaterial allows a single-stage reconstruction of extensive skull defect (120 cm(2)) in a previously infected area.