The screening of tumor-derived expression libraries for antigens which are recognized by high titered IgG antibodies present in autologous sera of the cancer patients by SEREX (serological identification of antigens by recombinant expression cloning) allows for the systematic identification of antigens in human cancers. SEREX has led to the definition of a plentitude of new tumor antigens in many different tumor entities. The majority of the antigens are encoded by hitherto unknown genes and can be grouped into different classes of antigens. The abundance of serologically defined human tumor antigens is not only of relevance for tumor biology and serodiagnosis of cancer, but also facilitates the identification of proteins recognized by tumor specific T lymphocytes, thus providing a molecular basis for polyvalent peptide-based and gene-therapeutic vaccine strategies in a wide variety of human neoplasms.