Scleroderma is a collagen vascular disease that can affect the soft tissues and bones resulting in calcifications, tissue atrophy, and osteolysis. It affects multiple organ systems and can also result in cardiovascular, renal, and gastrointestinal disease. In the musculoskeletal system, it primarily manifests in the distal extremities, resulting in coarse soft tissue calcification in the fingers and toes, soft tissue “whittling” at the tips of the digits, and acro-osteolysis. This chapter discusses imaging appearance and distribution of this disease.