Imaging modalities such as computed tomography (CT) are critical for monitoring musculoskeletal abnormalities in children with rare diseases. However, CT exposes patients to radiation, which limits its utility in the clinical setting, particularly during longitudinal evaluation. Synthetic CT is a novel, noncontrast, and rapid MRI method that can provide CT-like images without any radiation exposure and is easily performed in conjunction with traditional MRI, which detects soft-tissue and bone marrow abnormalities. To date, an evaluation of synthetic CT in pediatric patients with rare musculoskeletal diseases has been lacking. In this case series, the capability of synthetic CT to identify musculoskeletal lesions accurately in 2 rare disease patients is revealed. In Case 1, synthetic CT, in agreement with routine CT, identified an intraosseous lesion in the right femoral neck in a 16-year-old female with fibrous dysplasia, whereas standard-of-care MRIs additionally revealed mild surrounding edema-like bone marrow signal. For Case 2, synthetic CT applied to a 12-year-old female with fibrodysplasia ossificans progressiva revealed heterotopic ossification present along the cervical spine that had caused the fusion of multiple vertebrae. Our evaluation of synthetic CT offers important insights into the feasibility and utility of this methodology in children with rare diseases affecting the musculoskeletal system.