This chapter provides an in-depth exploration of disorders and neoplasms involving bones, joints, and soft tissues. A broad spectrum of primary bone tumors, such as osteosarcoma, chondroblastoma, and giant cell tumors, is analyzed, with a focus on their histopathological features and clinical implications. Specific conditions such as Paget disease of bone (PDB) and Ewing sarcoma are also discussed, shedding light on their molecular underpinnings and therapeutic challenges. The chapter highlights radiological findings, such as Codman’s triangle, which serve as critical diagnostic markers for bone lesions. Soft tissue tumors, including benign entities such as lipoma and more aggressive mesenchymal neoplasms such as mesenchymal chondrosarcomas, are reviewed to provide a comprehensive understanding of their presentation and management. Joint disorders such as crystal gout and pseudogout are addressed with emphasis on their pathophysiology and systemic impact. This chapter integrates pathology, imaging, and treatment strategies, offering a holistic approach to diagnosing and managing musculoskeletal disorders.