In this study, we have investigated the expression of the tumor antigen sperm protein 17 (SP17) in a large panel of human cancers and compared it with the expression of two well-characterized families of tumor antigens, melanoma-associated antigen-A (MAGE-A) and G antigen (GAGE). We found that SP17 was expressed in many cancer types with an overall frequency of 12%. SP17 was most frequently expressed in a different set of cancer types than MAGE-A and GAGE antigens and rarely overlapped with these proteins. Importantly, SP17 expression was limited to a small number of scattered cancer cells in most positive tumors in contrast to MAGE-A and GAGE proteins, which were homogenously expressed in large foci. Our results suggest that SP17 may not be an optimal target for cancer vaccines.