Fat tissue is a unique component of the soft tissue, and this fat tissue lies primarily in the spaces beneath the normal subcutaneous tissue, and within or around the organs. An entire lesion, or just a part of it, can be composed of these fat tissues. Therefore, it plays an important role in the diagnostic workup of suspected musculoskeletal diseases as well as in the differentiation between them. Fat tissue is shown as low density on plain radiographs, decreased attenuation on CT images, high signal intensity on T1-weighted images and it is hypoechoic on sonography. Because of its distinctive features, fat tissue is easy to verify on various modalities.?In addition, recent image studies like fat-suppressed imaging and STIR imaging provide more precise information of the lesion that involve fat tissue. In this article, we have reviewed the differentiation of musculoskeletal diseases, including the various tumorous lesion and tumor-like lesions involving the fat tissue.