To examine the imaging characteristics of intramuscular myxomas (IM) and myxoid liposarcomas (MLS) on 18F-FDG PET/CT and MRI. With IRB approval, our institutional imaging database was searched for pathologically proven IM and MLS evaluated by 18F-FDG PET/CT and MRI. PET/CT and MRI imaging characteristics were recorded and correlated with pathologic diagnosis. We found eight patients (2M, 6F) with IM (mean age 65.6 ± 10.4years) and 16 patients (7F, 9M) with MLS (mean age 42.8 ± 16.3years). MRI was availablein 7/8 IM and 15/16 MLS patients. There was no significant difference between the two groups in SUVmax (IM 2.7 ± 0.8, MLS 3.0 ± 1.0; p = 0.35), SUVmean (1.7 ± 0.4, 1.5 ± 0.5; p = 0.40), total lesion glycolysis (101.8 ± 127.3, 2420.2 ± 4003.3cm3*g/ml; p = 0.12), metabolic tumor volume (62.3 ± 71.1, 1742.9 ± 3308.0cm3; p = 0.17) or CT attenuation (p = 0.70). MLS occurred in younger patients (p = 0.0015), were larger (16.4 ± 8.2 vs. 5.6 ± 2.5cm; p = 0.0015), more often T1 hyperintense (p = 0.03), with nodular enhancement (p = 0.006), and macroscopic fat on CT (p = 0.0013) and MRI (p = <0.001) compared to myxomas. IM and MLS most commonly demonstrate low-grade FDG activity and overlapping metabolic measures on PET/CT. MRI is useful in differentiation, but MLS can present without macroscopic fat on MRI, underscoring the importance of radiologic-pathologic correlation for accurate diagnosis.