Cranial defects usually occur after trauma, neurosurgical procedures like decompressive craniotomy, tumour resections, infection and congenital defects. The purpose of cranial vault repair is to protect the underlying brain tissue, to reduce any localized pain and patient anxiety, and improve cranial aesthetics. Cranioplasty is a frequent neurosurgical procedure achieved with the aid of cranial prosthesis made from materials such as: titanium, autologous bone, ceramics and polymers. Prosthesis production is often costly and requires complex intraoperative processes. Implant customized manufacturing for craniopathies allows for a precise and anatomical reconstruction in a shorter operating time compared to other conventional techniques. We present a simple, low-cost method for prosthesis manufacturing that ensures surgical success. Two patients with cranial defects are presented to describe the three-dimensional (3D) printing technique for cranial reconstruction. A digital prosthesis model is designed and manufactured with the aid of a 3D computed tomography. Both the data of large sized cranial defects and the prosthesis are transferred to a 3D printer to obtain a physical model in poly-lactic acid which is then used in a laboratory to cast the final customised prosthesis in polymethyl methacrylate (PMMA). A precise compliance of the prosthesis to the osseous defect was achieved. At the 6 month postoperative follow-up no complications were observed i.e. rejection, toxicity, local or systemic infection, and the aesthetic change was very significant and satisfactory. Customized 3D PMMA prosthesis offers cost advantages, a great aesthetic result, reduced operating time and good biocompatibility.