Here we describe the findings of a unique example of the early techniques adopted in neurosurgery around 5000 years ago, consisting in a double well healed skull trephination associated with a post-cranial traumatic event occurring intra vitam to a young male from the Early Chalcolithic cemetery of Pontecagnano (South Italy, ca. 4,900 - 4,500 cal BP). Morphological, X-ray and 3D-CT scan skull-cap evaluation revealed that the main orifice was produced by scraping, obtained by clockwise rotary motion of a right-handed surgeon facing the patient, while the partial trephination was carried out by using a stone point as a drilling tool. In both cases, bone regrowth is indicative of the individual's prolonged postoperative survival and his near-complete recovery. The right femur shows a poorly healed mid-shaft fracture presumably induced by a high energy injury, and a resulting chronic osteomyelitis, affecting both femurs by hematogenous spread of the infection. Our observations on the visual and radiological features of skull and femur lesions, along with evidence on the timing of experimental bone regrowth vs. healing of lower limb fractures associated to long-term bone infections now suggest that this young man underwent a double skull trephination in order to alleviate his extremely painful condition induced by chronic osteomyelitis, which is thought to have been the cause of death.