The identification of tumor antigens, which are essential for the survival of tumor cells is a new avenue to prevent antigen loss variants emerging due to immunoselection, particularly during immune therapy. In the search for such immunogenic tumor antigens, we recently identified spontaneous cytotoxic lymphocyte (CTL) responses against the inhibitor of apoptosis protein survivin. Thus, we identified two HLA-A2-restricted, survivin-derived CTL epitopes, which both were targets for spontaneous CTL responses in melanoma, breast cancer, and CLL. Here, we extend these data and describe the characterization of novel HLA-A1-, HLA-A2-, HLA-A3-, and HLA-A11-restricted survivin epitopes on the basis of spontaneous CTL responses in cancer patients. These epitopes significantly increase the number of patients eligible for immunotherapy based on survivin derived peptides. Additionally, the collective targeting of several restriction elements is likely to decrease the risk of immune escape by HLA-allele loss.