Differential display-polymerase chain reaction was used to compare gene expression between human chondrosarcoma cell lines and normal cartilage. A new gene, CSAGE, has been cloned and belongs to a gene family that includes the taxol resistance associated gene (TRAG)-3. CSAGE, like TRAG-3, does not confer resistance to taxol when transfected in vitro. Both genes have alternatively spliced variants. CSAGE and TRAG-3 are expressed in chondrosarcoma, melanoma, and cartilage and testis, but not in other normal tissues. TRAG-3 has been reported to be a cancer/testis antigen. Our results suggest that CSAGE belongs to the growing list of cancer/testis antigens as well. In all of the CSAGE positive samples, the melanoma antigen gene family was also expressed. This is the first report on the expression of cancer/testis antigens in chondrosarcoma.