Sensitive techniques have recently been developed to identify tumoral antigens and to detect tumor-related autoantibodies in the peripheral blood of patients with cancer. Studies of these new methods indicate that the detection of a combination of autoantibodies could be a relevant prescreening strategy for the early detection of lung cancer in patients at high risk. Nevertheless, the clinical utility of autoantibodies for determining prognosis and monitoring response to systemic therapies in lung cancer is less conclusive. This article summarizes the clinical background and the technical aspects of current methods used for the detection and characterization of autoantibodies in blood, with a special focus on the implications of these methods for the clinical management of patients with lung cancer.