The skeleton can be affected by a wide variety of processes including infections, growth and development disturbances, circulatory disorders, metabolic diseases, reactive conditions, and neoplasms. All of these processes can occasionally produce a mass in bone that can clinically, radiographically and pathologically simulate a benign or malignant neoplasm. In this article, we discuss a select group of interesting metabolic and reactive lesions including brown tumor, osteomalacic fracture, hemophilic pseudotumor, reactive mixed mesenchymal pseudotumors of periosteal origin, avulsion injuries of bone, and pubic osteolysis, which are prone to be misinterpreted as neoplasms because of their peculiar clinical and morphologic features.