There is an urgent need to identify relevant tumor markers showing high sensitivity and specificity for early immunodiagnosis of breast cancer. Autoantibodies directed against tumor-associated antigens (TAAs) have been shown to be relevant tumor markers. The purpose of this study was to evaluate whether autoantibodies to a tumor-associated antigen p90/CIP2A can be used as diagnostic markers in breast cancer. In this study, autoantibody responses to p90/CIP2A were evaluated by enzyme-linked immunosorbent assay (ELISA), western blotting, and indirect immunofluorescence assay in sera from patients with breast cancer and normal human individuals. The results have demonstrated that p90/CIP2A can induce a relatively higher frequency of autoantibody response in breast cancer (19.1%) compared to the sera of normal individuals (2.3%). The frequency of p90/CIP2A expression in breast cancer tissues was significantly higher than that in adjacent normal tissues (P < 0.01). Our preliminary results suggest that autoantibodies against p90/CIP2A may be a useful serum biomarker for early stage breast cancer screening and diagnosis.