Several studies have demonstrated that sera from patients with cancer contain antibodies that recognize a unique group of autologous antigens called tumor-associated antigens (TAA). In the current study, we employed an immunoproteomic approach, combining 2DE, Western blot, and MALDI-MS to identify TAA in the sera of patients diagnosed with infiltrating ductal or in situ carcinoma breast cancer. Sera obtained from 25 newly diagnosed patients with stage II breast cancer and 20 healthy volunteers was evaluated for the presence of novel TAA. Alpha 1-antitrypsin (A1AT) antibodies were detected in 24 of 25 patients with breast cancer (96%) and in 2 of 20 controls (10%). Sensitivity of detection of autoantibodies against A1AT in patients with breast cancer was 96%. Our preliminary results suggest that A1AT and autoantibodies against alpha 1 antitrypsin may be useful serum biomarkers for early-stage breast cancer screening and diagnosis.