Abstract: Dedifferentiated chondrosarcoma (DDCS) comprises approximately10% of all chondrosarco-mas and has the worst outcome with a5-year survival of 10%. The preferred localizations are the femur, hu-merus and pelvis. DDCS represents a special form of chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with malignant mesenchymal tumor of high-malig-nancy grade. The diagnosis of DDCS is highly complicated, requiring detailed radiological and histopathologi-cal evaluation as well as precise bioptic technique. The dedifferentiated component is typically a high-grade sarcoma (usually grade 3 or 4), which can be either an osteosarcoma, a malignant fibrous histiocytoma or an anaplastic spindle cell sarcoma. In approximately one-third of the radiographs, one-third of the MR images, and one-half of the CT scans, the tumors demonstrates bimorphic features. Recently, array-based compara-tive genomic hybridization (array-CGH) studies have been performed on frozen chondrosarcoma (including DDCS) specimens. There is a statistically significant association between high-grade tumor (grade Ⅲand de-differentiated) and the recurrent genetic deletions at 5q14.2~q21.3, 6q16~q25.3, 9p24.2~q12, and 9p21.3. One of the most commonly deleted regions of DDCS involved chromosome 9. Earlier investigations of DDCS showed p 53 mutation and p53-LOH in the anaplastic component. It is also accompanied by Rb-LOH. P16INK 4 and E-cadherin promotor methylation were observed in the low grade chondroid compartment of DDCS. While p16INK 4, FHIT, and E-cadherin were methylated in highly malignant osteosarcomatous com-partment of the tumor. Surgical resection of the tumor within wide or radical margins is the most important treatment. The value of neoadjuvant or adjuvant therapy remain uncertain. Several new drug targets have been identified and phase Ⅱstudies are currently ongoing. Current phase Ⅱtrials open for DDCS patients used the following medicine: apomab (proapoptotic selective agonist of Apo 2L/TRAIL death receptor), perifos-ine (serine/threonine kinase Akt inhibitor), dasatinib (multitargeted small-molecule tyrosine kinase inhibitor), and the combination of gemcitabine and docetaxel. More recently, several phaseⅠstudies have reported in -cidental responses of DDCS to newer targeted agents, such as histone deacetylase and vascular endothelial growth factor antisense oligodeoxynucleotide. The prognosis for patients with DDCS remains poor. The poor prognosis of the DDCS is determined by nonchondroid high grade component caused by invasive growth and formation of metastases. Therefore, early diagnosis and prompt surgical treatment may improve the outcome.