Non-neoplastic bone lesions represent a heterogeneous group of conditions that stem from reactive, genetic, or metabolic processes. These lesions can sometimes closely mimic malignant tumors, posing diagnostic challenges. This article focuses on a few non-neoplastic bone lesions and their differential diagnoses, including florid reactive periostitis, Paget disease of bone, fractures (including compression/stress fractures), and melorheostosis, each of which exhibits distinct clinical, radiological, and pathologic features. Unlike neoplastic processes of bone, no specific immunohistochemical features or molecular studies are helpful in diagnosing these lesions. In many cases, the diagnosis is based primarily on the radiographic findings, often eliminating the need for a biopsy.