During the development of tumors, autoantibodies against aberrant or overexpressed autoantigens can be induced. Several hundreds of tumor-associated autoantibodies (TAAB) with more or less specificity for tumors have been found until now by molecular cloning and proteomics technologies. Many TAAB are detectable in preclinical stages of the disease and may be indicators of tumor development. The screening for autoantibody responses in tumor patients may lead to new diagnostic tumor markers and may be a simple and effective way to identify concomitantly cytotoxic T-lymphocyte (CTL) reactivity. However, most of the TAAB lack sufficient sensitivity and specificity for use as biomarkers in the clinical practice. For further use TAAB should be selected for their specificity regarding malignancies and for their potential clinical application. If selected for high specificity, for the screening of risk groups the sensitivities of most TAAB are too low. A combined determination of two or more tumor-specific autoantibodies may overcome this problem. Therefore, a further evaluation of the relevance of known autoantibody specificities as well as the search for novel diagnostically relevant TAAB by different methodologies is necessary. An optimal combination of highly specific TAAB in multiparametric assays as well as the standardization of the autoantibody analysis is necessary to exhaust the potential of TAAB in the early (presymptomatic) diagnosis and monitoring of malignancies.