The efficacy of current standard therapies for the treatment of sarcoma remains limited. With the aim of identifying target antigens relevant to the development of vaccine-based immunotherapy of sarcoma, we have addressed the relevance of tumor-specific antigens encoded by genes belonging to the SSX family as vaccine targets in sarcoma tumors. Expression of SSX-1 to -5 was analyzed in a collection of sarcoma tumors of diverse histological subtypes and in sarcoma cell lines. We found expression of at least one SSX-encoded antigen in 42% of sarcoma tumors, including 5 of 7 different histological subtypes, and in 50% of sarcoma cell lines. SSX-1 was the most frequently expressed family member, followed by SSX-4, -2 and -5. Expression of SSX-3 was detected in only one sample. Importantly, most SSX positive samples co-expressed more than one family member. In addition, assessment of CD8+ T cell recognition of HLA-A2+ SSX-2+ sarcoma cells showed that the latter were efficiently recognized and lysed by SSX-2-specific CTLs. The results of this study indicate that SSX antigens are relevant targets for the development of vaccine-based immunotherapy of sarcoma and encourage the start of vaccination trials using SSX-derived immunogens in sarcoma patients.