ΣS is a measure of the disulfide bonds and free thiol groups of serum immunoglobulin (Ig) G, as determined by the reaction with dithionitrobenzoate. Significant decreases of 2S previously were detected in malignant compared with benign diseases of various organs. This study shows the application of ΣS for the diagnosis of breast cancer. The following results were obtained. First, 132 patients with benign breast diseases showed a ΣS of 1.48 ± 0.29 (standard deviation) per mole IgG; this was not different from 1.51 ± 0.36 found in 182 controls. In contrast, IgG from 198 patients with primary breast carcinoma of all four stages (tumor‐node‐metastasis system) gave a ΣS of 1.22 ± 0.29, a significant (P less than 0.0001) decrease of ΣS from benign to malignant breast disease. Second, ΣS values of single Stages I, II, III, and IV, were 1.27 (n = 59), 1.23 (n = 83), 1.19 (n = 35), and 1.10 (n = 21), respectively, each significantly different from ΣS in benign disease and showing a decreasing trend with increasing tumor progress. Differences were significant between Stages I and IV (P less than 0.025) and II and IV (P less than 0.05). Third, 63% of Stage I breast carcinoma patients had ΣS values below a critical threshold of 1.38. This serum positivity rose to 90% in Stage IV. These values exceeded those reported with other tumor markers. The overall power of ΣS to distinguish between benign and malignant breast disease had a specificity of 61% and a sensitivity of 78%. Early stages (I and II) of breast cancer could be distinguished from benign diseases with 64% specificity and 69% sensitivity. Advanced Stage IV could be discriminated from early Stages I and II with 55% specificity and 71% sensitivity. Thus, the analysis of ΣS may significantly contribute to the surveillance of patients with breast cancer.