Osteosarcoma is the most common primary bone malignancy in skeletally immature patients. The proximal humerus is the third most common site of osteosarcoma. The literature shows a paucity of published data concerning the outcome of proximal humerus osteosarcoma managed by limb salvage. The purpose of this study was to answer the following questions: (1) do patients with proximal humerus osteosarcoma managed by limb salvage and neoadjuvant chemotherapy show good functional and oncological outcomes, and (2) are there any prognostic factors that are associated with better oncological and functional outcomes? The study was a retrospective case series study assessing the overall outcome of 34 patients with proximal humerus osteosarcoma. Eighteen patients were males (53%) while 16 were females. Biological reconstruction was done in 15 patients (44%), while nonbiological reconstruction was done in 19 patients. Resections were mainly intraarticular (82%). Functional outcome was assessed using the Musculoskeletal Tumor Society (MSTS) score, while oncological outcome was assessed based on local recurrence and development of chest metastasis. Comparisons between quantitative variables were done using the nonparametric Mann-Whitney test. To compare categorical data, the chi-square (χ2) test was performed. The exact test was used instead when the expected frequency was less than 5. Correlations between quantitative variables were examined using the Spearman correlation coefficient. The mean MSTS score was 25.5 (range 23-29). A younger age was statistically correlated with a poorer MSTS score (P = 0.0016). Six patients out of 34 (17.6%) had local recurrence and four of them (67%) were treated by forequarter amputation. 41% of patients developed chest metastasis, and the majority of them were treated by chemotherapy (71%). In comparison with patients with osteosarcoma at other sites who were also managed in our institution, proximal humerus osteosarcoma patients showed higher incidence rates of local recurrence and chest metastasis along with lower 5-year patient and limb survivorships compared to distal femur, proximal tibia and proximal femur osteosarcoma patients. Treatment of osteosarcoma of the proximal humerus by limb salvage and chemotherapy yields a good functional outcome. The method of reconstruction does not impact the resultant function. The 5-year survivorship of these patients is 65%. Younger patients have a better oncological outcome and an inferior functional outcome. Level IV therapeutic study.