Metabolic bone disease represents a distinct category of disorders pertaining to mineral imbalances and bone metabolism that conventionally includes osteoporosis, osteomalacia, hyperparathyroidism, and Paget’s disease. Paget’s disease is discussed in another chapter (see Chapter 28). The three other entities will be discussed as they pertain to tumor-like lesions of the bone. Osteoporosis is characterized by fractures which in the vertebrae and pelvis could be mistaken for a more sinister disease such as metastases. Exuberant callus formation in OI type V should not be mistaken for sarcoma. Oncogenic osteomalacia is a rare clinicopathological syndrome characterized by a triad of severe hypophosphatemia, hyperphosphaturia, and osteomalacia secondary to a neoplasm. The condition is challenging to diagnose, as the patient usually presents with symptoms of osteomalacia and the primary mesenchymal tumor may be small and often asymptomatic. However, correct diagnosis is gratifying as surgical removal of the offending tumor can lead to dramatic reversal of osteomalacia. With the increased life span of hemodialysis patients, radiologists are more likely to encounter brown tumors as well as musculoskeletal manifestations of β2-microglobulin-associated amyloidosis including lytic osseous lesions (amyloidomas) and renal spondyloarthropathy, and these conditions should not be mistaken for primary or secondary bone neoplasms. Reactive lesions of the bone that may mimic bone tumors include florid reactive periostitis and chronic nonbacterial osteitis.