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CIC-DUX4 sarcoma is highly aggressive and rapidly develops lethal metastatic disease and chemoresistance. Its histology is similar to that of Ewing sarcoma and other small round cell sarcomas. Correlation with clinical data, radiological findings, pathological results (including immunohistochemistry and fluorescence in situ hybridization), and/or molecular techniques is necessary. We present the case of a 44-year-old woman who was initially diagnosed as having high-grade undifferentiated round cell sarcoma confirmed to be a CIC-DUX sarcoma by next-generation sequencing.