Abstract: Objective: To investigate the differential expression of Sox9 in conventional chondrosarcoma, dedifferentiated chondrosarcoma and normal cartilage. Methods: We reported12cases of chondrosarcomas, which were initially diagnosed as chondrosarcomas ( 6 cases of conventional chondrosarcoma and 6 cases of dedifferentiated chondrosarcoma) at Peking University People's Hospital between January 2003 and January 2007. We used genechip method to identify differentially expressed genes involved in conventional chondrosarcoma, dedifferentiated chondrosarcoma and in normal cartilage (6 cases) and found thousands of differentially expressed genes after extensive statistical analysis. With Sox 9 which played crucial roles in the process of both differentiation and maturation of chondrocyte as a candidate, we used Real-time PCR, Western blot and immunohistochemistry to confirm the results found by gene chip. Results: DNA microarray results showed that Sox9 was up-regulated about 1.6 times in conventional chondrosarcoma compared with that in normal cartilage. But in dedifferentiated chondrosarcoma, the expression level of Sox9 was significantly down-regulated,0.082 times of that in normal cartilage. Real-time PCR results showed that the expression levels of Sox9 mRNA in conventional chondrosarcomas and dedifferentiated chondrosarcomas were 1.68±0.119 and 0.088 ±0.017 , respectively. Sox 9 protein level was significantly higher in human conventional chondrosarcomas than that in normal cartilage. Sox 9 protein level in dedifferentiated chondrosarcomas was significantly lower than that in normal cartilage tissue. All of the 6 cases of conventional chondrosarcomas showed diffuse and strong staining of Sox 9. However, Only scattered staining was observed in dedifferentiated chondrosarcomas. Conclusion:Compared with that in normal cartilage, Sox 9 expression is up-regulated in conventional chondrosarcomas and down regulated in dedifferentiated chondrosarcomas. Decrease of Sox 9 expression in dedifferentiated chondrosarcoma is correlated with poor survival, indicating that Sox 9 may serve as a molecular prognostic marker for chondrosarcomas and disease progression.