Our recent work demonstrated that circulating levels of IgG antibody to linear peptide antigens derived from annexin A1 (ANXA1) were significantly increased in lung cancer. The present study was then undertaken to test whether circulating anti-ANXA1 antibodies were also altered in breast cancer. An enzyme-linked immunosorbent assay was developed in-house to determine circulating IgG against ANXA1-derived peptide antigens in 152 female patients with breast cancer and 160 female control subjects. Student's t test revealed that patients with breast cancer had significantly higher levels of anti-ANXA1 IgG than control subjects (t = 4.75, P < 0.0001). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.73 with 95% confidence interval (CI) 0.67-0.78, and the sensitivity of anti-ANXA1 IgG assay was 23.2% against the specificity of 90%. The levels of anti-ANXA1 IgG did not appear to be stage-dependent, and Pearson correlation analysis showed no correlation between the anti-ANXA1 IgG levels and the stages of breast cancer (r = -0.02, df = 149, P = 0.796). This work suggests that circulating IgG for ANXA1-derived peptide antigens may have both diagnostic and prognostic values for breast cancer although further screening is needed to identify more such peptide antigens derived from tumor-associated antigens.