Six patients underwent segmental bone resection and limb salvage surgery for primary or metastatic bone tumors involving the diaphysis of the femur, the tibia, and the humerus using a modular intramedullary diaphyseal segmental defect fixation system. There were four men and two women with a mean age of 62 years (range: 40-77 years). Histological diagnosis included adamantinoma, synovial sarcoma, multiple myeloma, metastatic renal cell carcinoma, myeloid carcinoma of the thyroid gland, and adenocarcinoma of the stomach. The mean follow-up was 17 months (range: 11-28 months). At the latest examination, five patients were free of local or distant disease and one patient had deceased with distant disease, without evidence of local recurrence. Revision surgery was necessary in one patient because of mechanical loosening of the proximal fixation of the prosthesis at 24 months. The mean postoperative increase of the Enneking rating score was 87.8%. The intramedullary diaphyseal segmental defect fixation system used herein is associated with a satisfactory functional and oncological outcome after wide resection of diaphyseal bone tumors.