Background: Retroperitoneal sarcomas (RPS) are rare findings that can grow into large masses without eliciting severe symptoms. Nowadays surgical resection is the only radical therapy, whenever possible. We present two consecutive cases of RPSs that resulted in dedifferentiated liposarcomas (DDLPS) and underwent R0 surgical resection with and without a nephron-sparing procedure. The diagnostic workup, the surgical approach, the impact of late surgical management due to the COVID pandemic, and the latest literature on the topic will be discussed and analyzed. Case Presentation: The patients, who refused to undergo any medical examination during the prior two years due to the COVID pandemic, were admitted to our Institution complaining about weight loss and general abdominal discomfort. In the first case, we observed a primitive giant abdominal right neoplasm of retroperitoneal origin enveloping and medializing the right kidney. The second patient had a similar primitive retroperitoneal giant left neoplasm which didn’t affect the kidney. Given the masses’ characteristics and the absence of distant metastases, after a multidisciplinary discussion, radical surgical removal was carried out for both patients. The lesions appeared well-defined from the surrounding tissues, and significantly compressed all the adjacent organs, without signs of infiltration. In the first patient, the right kidney was surrounded and undetachable from the tumor and it was removed en bloc with the mass. The second patient benefited from a nephron-sparing resection, thanks to the existence of a clear cleavage plane. The postoperative courses were uneventful. Both the histological examinations were oriented towards a DDLPS. And both patients were addressed with adjuvant chemotherapy. Conclusions: The treatment of giant RPS is still challenging and requires multidisciplinary treatment as well as, when possible, radical surgical removal. The lack of tissue infiltration and the avoidance of major organs’ excision or reconstruction (including the kidney) could lead to an easier postoperative course and a better prognosis. When possible, surgical management of recurrences or incompletely resected masses must be pursued. As the COVID pandemic caused limited medicalization of many population groups and delayed diagnosis of other oncologic diseases, an increased number of DDLPSs could be expected in the near future.

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