Objective: To investigate the clinical features, pathological features and differential diagnosis of Castleman’s disease of the retroperitoneum with strange-shaped cells, so as to reduce misdiagnosis. Methods: The clinical data of 1 case of Castleman 's disease of the retroperitoneum with strange-shaped cells admitted to our hospital were retrospectively analyzed and the literature was reviewed. Results: The patient came to the hospital with abdominal distension and discomfort for more than half a year. CT examination showed that a large retroperitoneal mass, and retroperitoneal tumor resection was considered for liposarcoma. Postoperative pathological examination showed that the number of lymphoid follicles increased, the mantle area widened, germinal center atrophy, a large number of plasma cells and a few lymphocytes between follicles in the background could be seen scattered strange-shape large cells. Immunohistochemical staining showed that CD3, CD5, CD38, CD20 and CD21 were all (+), and CyClinD1 (-), Kappa and Lambda were all (+). The patient was diagnosed as Castleman’s disease of the retroperitoneum, and was discharged from hospital with recovered well after surgery. After 9 months of follow-up, no obvious signs of recurrence were found. Conclusion: Castleman's disease with strange-shaped cells is rare, and the lack of understanding of strange-shaped cells can easily be misdiagnosed as malignant tumors, leading to overtreatment. The signs and imaging examinations are lack of specificity. Timely histopathological examination is the key to avoid misdiagnosis.