Biomarkers for preclinical diagnosis of cancer are valuable tools for detection of malignant tumors at earlystages in groups at risk and screening healthy people, as well as monitoring disease recurrence after treatment ofcancer. However the complexity of the body’s response to the pathological processes makes it virtually impossibleto evaluate this response to the development of the disease using a single biomarker that is present in the serum atlow concentrations. An alternative approach to standard biomarker analysis is called immunosignature. Insteadof going after biomarkers themselves this approach rely on the analysis of the humoral immune response tomolecular changes associated with the development of pathological processes. It is known that antibodies areproduced in response to proteins expressed during cancer development. Accordingly, the changes in antibodyrepertoire associated with tumor growth can serve as biomarkers of cancer. Immunosignature is a highlysensitive method for antibody repertoire analysis utilizing high density peptide microarrays. In the presentreview we discuss modern methods for antibody detection, as well as describe the principles and applicationsof immunosignature in research and clinical practice.