Radiography offers more information than any other imaging modality in the study of bone lesions and remains the cornerstone for the differential diagnosis of skeletal tumors and tumor-like lesions thanks to its higher specificity in detecting tumor morphologic hallmarks. the radiographic features that help the radiologist make the diagnosis of a bone tumor or tumor-like lesion, or at least narrow the diagnostic possibilities, include patterns of bone destruction (geographic, moth-eaten and permeated), lesion margins (from sclerotic rim to ill-defined margin), internal characteristics of the lesion (non-matrix producing tumors, non-mineralized matrix producing tumors, mineralized matrix producing tumors), type of host bone response (medullary or periosteal), location (femur, tibia, humerus, etc.), site (metaphysis, diaphysis or epiphysis), and position (central, eccentric or periosteal) of the lesion in the skeletal system and in the individual bone, soft tissue involvement, and single or multiple lesion nature. Patterns of bone destruction, margins, and reactive changes in the host bone clearly depict the growth rate of a bone lesion, that is its biologic activity; the matrix of the lesion, as well as lesion location, site and position may allow a specific diagnosis. This general information coupled with clinical information helps define whether the lesion is neoplastic or non-neoplastic, benign or malignant, primary or metastatic, and will help further direct the subsequent work-up. CT may be indicated for the optimal assessment of tumor matrix especially in complex anatomical sites, such as the spine, pelvis and hindfoot. The main role of MRI lies in local tumor staging, especially for planning limb-salving resections. Biopsy is the definitive diagnostic procedure and should be carried out only after the appropriate diagnostic and staging tests. Whenever a bone lesion is suspected, clinical-radiologic pathologic correlation is essential to make a more accurate diagnosis and to improve patient care.