Several bone and soft-tissue conditions can transform into malignancy. This carcinogenesis can occur in benign bone and soft-tissue tumors, as well as in tissue injured by radiation, infection, or trauma. These conditions include common tumors and diseases such as osteochondroma, enchondroma, osteomyelitis, and osteonecrosis; however, other entities are more rare. Because many of these conditions are assessed at surveillance imaging, changes in the size and shape of the lesion and the development of aggressive features are often first identified by the radiologist. It is important to be knowledgeable of these conditions and their characteristic imaging appearances so that cases of malignant transformation can be identified early and appropriate treatment can be initiated. The authors outline the key imaging features and clinical considerations that can indicate a premalignant state, providing a rationale for more aggressive monitoring and/or intervention. This review underscores the necessity of advanced imaging modalities for enhancing diagnostic accuracy, which is paramount for improving patient prognoses and reducing the morbidity associated with premalignant bone and soft-tissue conditions. ©RSNA, 2025 Supplemental material is available for this article.