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Introduction: The humerus is a relatively common location of malignant bone tumor in general and Ewing sarcoma in particular. However, total humerus replacement after humeral tumor resection is still a fairly rare and challenging surgery for surgeons. Case presentation: A 14-year-old man was diagnosed with Ewing sarcoma. The patient underwent a total humerus replacement and neoadjuvant chemotherapy before and after the surgery. At 6 months post-operative, he was able to return to normal activities with good hand and elbow functions, although limited shoulder movement. MSTS score was 76.7%. There were no significant complications as well as local recurrence or metastasis. Conclusion: Total humerus replacement surgery for the patient of Ewing sarcoma of the humerus had initial positive results. However, the patient needs to follow up longer to evaluate the complications related to the prosthesis as well as the recurrence and metastasis of the tumor.