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In spinal surgery, 3D prothesis represents a useful instrument for spinal reconstruction after the removal of spinal tumors that require an “en bloc” resection. This represents a complex and demanding procedure, aiming to restore spinal length, alignment and weight-bearing capacity and to provide immediate stability. Thus, in this systematic review the authors searched the literature to investigate and discuss the advantages and limitations of using 3D-printed custom-made vertebral bodies in the treatment of spinal tumors. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, with no limits in terms of date of publication. The collected studies were exported to Mendeley. The articles were selected according to the following inclusion criteria: availability of full articles, full articles in English, studies regarding the implant of 3D custom-made prothesis after total or partial vertebral resection, studies regarding patients with a histologically confirmed diagnosis of primary spinal tumor or solitary bone metastasis; studies evaluating the implant of 3d custom-made prothesis in the cervical, thoracic, and lumbar spine. Nineteen published studies were included in this literature review, and include a total of 87 patients, 49 males (56.3%) and 38 females (43.7%). The main tumoral location and primary tumor diagnosis were evaluated. The 3D custom-made prothesis represents a feasible tool after tumor en-bloc resection in spinal reconstruction. This procedure is still evolving, and long-term follow-ups are mandatory to assess its safeness and usefulness.