Background: Six cell surface receptors, human epidermal growth factor receptor (Her)-2, platelet-derived growth factor receptor (PDGFR)-β, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR), c-Met, and vascular endothelial growth factor receptor (VEGFR)-3, previously demonstrated variable expression across varying osteosarcoma (OS) cell lines. The current study sought to validate previous expression patterns and evaluate whether these receptors offer prognostic and therapeutic value. Methods: Patient-derived OS samples (n = 52) were labeled with antibodies to Her-2, PDGFR-β, IGF-1R, IR, c-Met, and VEGFR-3. Expression was characterized using flow cytometry. The geometric mean fluorescent intensity (geoMFI) for each receptor was calculated relative to a negative control. The event-free survival (EFS) and overall survival for patients with positive receptor expression were estimated by the Kaplan-Meier method. Differences in hazard for EFS event and overall survival event for patients with positive receptor expression were assessed using the log-rank test. Results: All 6 receptors were variably expressed in the majority of cell lines. None of the 6 receptors, were found to be significant predictors of EFS or overall survival. The sum total number of positive receptors per cell line also failed to predict EFS or overall survival. Conclusion: The six cell surface receptors demonstrated variable expression across the majority of patient-derived OS samples tested. While receptor expression did not provide prognostic value, their consistent expression makes them attractive targets for future therapeutic approaches.