This article reviews recent molecular, biologic, therapeutic, and clinical findings in dedifferentiated chondrosarcoma. Dedifferentiated chondrosarcoma is one of the most malignant primary bone tumors characterized by two distinct histopathologic components: a well-differentiated chondral lesion sharply juxtaposed with a high-grade noncartilaginous component. Wide or radical surgical resection is mandatory. High-dose radiation therapy is confined to inaccessible sites and palliation. Chemotherapy is administered whenever the dedifferentiated component is chemosensitive and the patient is in good general condition. Despite this approach, metastases will result in poor survival of these patients.