Objective ·To analyze the clinical, pathological and molecular genetic characteristics of CIC-rearranged sarcoma (CRS) in children to improve the understanding of small round cell sarcoma newly proposed in the 5th edition of the WHO Classification of Soft Tissue and Bone Tumours. Methods ·Data of 54 patients with small round cell undifferentiated sarcoma diagnosed in Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine from January 2019 to April 2021 were collected. Five cases of pediatric CRS with complete clinical, imaging, pathological and follow-up data were selected to analyze their clinicopathological features. Results ·There were 3 males and 2 females in the 5 CRS patients aged from 5 months to 10 years. There were 3 asymptomatic children, and chest and back pain and projectile vomiting were the first symptoms in 2 cases respectively. All CT images showed cystic, solid or mixed irregular soft tissue masses of varying sizes. Histopathological examination showed that the average maximum diameter of the tumor was 12.5 cm, and the cut surface was grayish white or grayish brown, with the appearance of rotten fish flesh. The histopathology was mainly distributed in small round diffuse sheets. Immunohistochemistry showed CD99 diffuse membrane positive or focal positive, WT1 diffuse nuclear positive, and BCL2, CD56, FLI1 and ERG expressed to varying degrees. Fluorescence in situ hybridization (FISH) test showed that EWSR1 (22q12) was negative and CIC (19q13) gene was rearranged. Meanwhile, some children also had CIC fusion gene mutations, including 2 CIC-DUX4 fusion cases and 1 CIC-NUTM1 fusion case. All patients were treated with surgery and postoperative adjuvant chemotherapy. Follow?up data were available in all the five cases (mean 21.4 months); one patient died of disease, whereas two patients were alive with unresectable recurrent tumour, and the remaining two patients were alive with no evidence of disease. Conclusion ·Pediatric CRS is a rare malignant soft tissue tumor with asymptomatic or non-specific symptoms, easy metastasis and poor prognosis. Immunohistochemistry combined with EWSR1 and CIC rearrangement-related molecular examination is helpful for the diagnosis of Ewing's sarcomatoid soft tissue tumors, and further detection of CIC fusion gene may be helpful for prognosis estimation.