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Background: Retroperitoneal liposarcoma is a rare and complex tumor originating from the mesenchymal tissues, with no specific manifestations in the early stage, and a large tumor size in the late stage. Patients often consult a physician because of large abdominal mass, increased abdominal circumference, and abdominal pain, and rarely because of leukocytosis., Patient Concerns: A 54-year-old female presented to our hospital with complaints of "abdominal distension for over 3 months, left lumbar pain for over 2 months." Considering the comprehensive symptoms, examinations, computed tomography scans, and pathological results, the possibility of retroperitoneal liposarcoma is high., Diagnoses: Retroperitoneal liposarcoma with leukocytosis., Interventions: Open retroperitoneal mass excision along with transcystoscopic left ureteral Double-J Ureterl Stent Insertion tube placement and left nephrectomy., Outcomes: The postoperative pathological findings of the abdominal mass, combined with morphological and immunohistochemical results, are consistent with retroperitoneal liposarcoma. The patient had no recurrence in 7 months of postoperative follow-up conducted on the telephone and is now in continued follow-up., Conclusion: Retroperitoneal liposarcoma is highly malignant and prone to recurrence. Radical surgery is currently the primary treatment modality for patients with this condition. Analogous to cancer patients, those with elevated white blood cell counts and retroperitoneal liposarcoma may have poor prognoses, with a high likelihood of local recurrence and distant metastasis. Close postoperative follow-up is necessary. Therefore, regular postoperative review of blood routine may be a relatively economical and convenient method for the early detection of recurrence and metastasis of retroperitoneal liposarcoma., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)