Aim: Retroperitoneal soft-tissue sarcomas are relatively uncommon diseases, and the most frequent histotype, ranging from 20 to 45% of all cases, is represented by liposarcoma, which is a hard-to-treat condition for its local aggressiveness and clinical aspecificity. Presentation of case: We report a case of a 69-year-old woman who underwent surgical resection for a giant pleomorphic retroperitoneal liposarcoma. Discussion: Currently, chemotherapy for retroperitoneal soft-tissue sarcomas is not effective, and radiotherapy has limited efficacy due to the toxicity affecting adjacent intra-abdominal structures and showed validity only in case of high-grade malignancy by reducing local recurrence but with no advantage in overall survival. Nowadays, complete surgical resection remains the most important predictor of local recurrence and overall survival. Conclusion: The removal of a retroperitoneal sarcoma of remarkable size is a challenge for the surgeon owing to the anatomical site, the absence of an anatomically evident vascular-lymphatic peduncle, and the adhesions contracted with the contiguous organs and great vessels. Therefore, we believe that, particularly for large-sized diseases associated with high-grade malignancy, a complete surgical resection with the removal of the contiguous intra- and retroperitoneal organs when infiltrated represents the only therapeutic option to obtain a negative margin and therefore an oncological radicality.