Cancer/testis antigens (CTA) are an expanding family of immunogenic proteins selectively expressed in human neoplasms. As little is known about the expression of serologically identified CTA in leukemias so far, we investigated the expression of 5 CT genes (SSX-1, HOM-MEL-40/SSX-2, HOM-TES-14/SCP-1, SCP-3 and NY-ESO-1) in leukemic blood samples obtained from patients with either acute lymphatic leukemias (ALL) or myelocytic leukemia (AML). RT-PCR-analyses showed no expression of any of the CT-genes in the leukemia samples of 19 patients with AML, whereas frequent expression was found in ALL. In the 17 ALL cases studied, SCP3a, SSX-1, HOM-MEL-40/SXX-2 and HOM-TES-14/SCP-1 were expressed in 47, 29, 29 and 12%, respectively, whereas no case was positive for NY-ESO-1. 65% of patients with ALL showed expression of at least one, 41% of two or more of the five CT-genes investigated. We conclude that a majority of the ALLs might be amenable for specific immunotherapeutic interventions. However, the identification of additional antigens with a frequent expression in leukemias is warranted to allow the development of widely applicable polyvalent leukemia vaccines.