Design and processing capabilities of additive manufacturing (AM) to fabricate complex geometries continues to drive the adoption of AM for biomedical applications. In this study, a validated design methodology is presented to evaluate AM as an effective fabrication technique for reconstruction of large bone defects after tumor resection in pediatric oncology patients. Implanting off-the-shelf components in pediatric patients is especially challenging because most standard components are sized and shaped for more common adult cases. While currently reported efforts on AM implants are focused on maxillofacial, hip and knee reconstructions, there have been no reported studies on reconstruction of proximal humerus tumors. A case study of a 9-year-old diagnosed with proximal humerus osteosarcoma was used to develop a patient-specific AM prosthesis for the humerus following tumor resection. Commonly used body-centered cubic (BCC) structures were incorporated at the surgical neck and distal interface in order to increase the effective surface area, promote osseointegration, and reduce the implant weight. A patient-specific prosthesis was fabricated using electron beam melting method from biocompatible Ti-6Al-4V. Both computational and biomechanical tests were performed on the prosthesis to evaluate its biomechanical behavior under varying loading conditions. Morphological analysis of the construct using micro-computed tomography was used to compare the as-designed and as-built prosthesis. It was found that the patient-specific prosthesis could withstand physiologically-relevant loading conditions with minimal permanent deformation (82 μm after 105 cycles) at the medial aspect of the porous surgical neck. These outcomes support potential translation of the patient-specific AM prostheses to reconstruct large bone defects following tumor resection.