Autoantibodies against autologous tumor-associated antigens have been detected in the asymptomatic stage of cancer and can thus serve as biomarkers for early cancer diagnosis. Moreover, because autoantibodies are found in sera, they can be screened easily using a noninvasive approach. Consequently, many studies have been initiated to identify novel autoantibodies relevant to various cancer types. To facilitate autoantibody discovery, approaches that allow the simultaneous identification of multiple autoantibodies are preferred. Five such techniques--SEREX, phage display, protein microarray, SERPA and MAPPing--are discussed here. In the second part of this review, we discussed autoantibodies found in the five most common cancers (lung, breast, colorectal, stomach and liver). The discovery of panels of tumor-associated antigens and autoantibody signatures with high sensitivity and specificity would aid in the development of diagnostics, prognostics and therapeutics for cancer patients.