Second malignant neoplasms (SMNs) are being increasingly recognized. This report describes a case of a 7-year-old girl with a history of acute lymphoblastic leukemia (ALL) who presented with a mass in her humerus that was diagnosed as Ewing sarcoma. Second malignant neoplasms are relatively rare in survivors of ALL treated without radiation. Even more unusual is the development of Ewing sarcoma as the SMN.