Gene rearrangements involving the Ewing sarcoma breakpoint region 1 (EWSR1) gene are seen in a broad range of sarcomas and some nonmesenchymal neoplasms. Ewing sarcoma is molecularly defined by a fusion of the EWSR1 gene (or rarely the related FUS gene) to a member of the E26 transformation-specific (ETS) family of transcription factors, frequently the EWSR1-FLI1 fusion. More recently, EWSR1 gene fusion to non-ETS family members, including the nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 2 (NFATC2) gene, has been reported in a histological variant of Ewing sarcoma. Here, we report a malignant round cell tumor of bone with an EWSR1-NFATC2 fusion gene. This report builds upon the unusual morphological and clinical presentation of bone neoplasms containing an EWSR1-NFATC2 fusion gene.