Objective <p>Myxoid liposarcoma is a soft tissue sarcoma with a unique predilection for metastasis to atypical sites compared to other soft tissue sarcoma histologic subtypes. Does a whole-body (PET/MRI or PET/CT) staging approach, compared to current National Comprehensive Cancer Network (NCCN) guidelines, improve our ability to identify metastatic disease in myxoid liposarcoma?</p> Materials and methods <p>A retrospective analysis identified 31 patients diagnosed with myxoid liposarcoma between 2015 and 2022. Ten patients were staged with standard guidelines and 21 with a whole-body PET modality. Patients who did not complete any staging or had their definitive care performed outside our institution were excluded.</p> Results <p>In the whole-body group, three (14.3%) patients were found to have metastatic disease on initial presentation, while none had metastatic disease in the standard group. During post-treatment surveillance, two patients in the standard group (<i>n</i> = 10) had new metastases discovered by CT chest with/without MRI spine. Three patients in the whole-body group developed new metastases, which were discovered by whole-body PET/MRI in one and MRI spine in two patients. The median SUVmax of the primary tumor site was 2.8 (range 2.3, 3.4), and for metastasis detected on follow-up imaging, the median SUVmax was 3.2 and 2.6 for the whole-body and standard groups, respectively.</p> Conclusions <p>Whole-body PET modalities for staging myxoid liposarcoma appear to detect initial metastatic disease and new disease during surveillance, at least as well as current NCCN guideline–recommended modalities. Given that the avidity of myxoid liposarcoma is low, the added value of PET imaging may be limited.</p>