The prevalence of thyroid peroxidase autoantibodies (TPO.Ab) was assessed in patients with either breast carcinoma or benign breast disease, and its association with disease outcome in breast carcinoma was studied. TPO.Ab were detected by direct RIA in serum from 121/356 (34.0%) of patients with breast carcinoma, compared with 36/194 (18.5%) of controls (P < 0.001); and in 31/108 (28.7%) with benign breast disease, compared with 12/88 (13.6%) of controls (P < 0.05). Survival analysis in a group of 142 women with breast carcinoma demonstrated that TPO.Ab titres > or = 0.3 U/mL were associated with a significantly better disease-free [relative risk (RR) = 1.84, P < 0.05] and overall survival (RR = 3.46, P < 0.02), compared with those who were TPO.Ab-negative. Better outcome associated with higher TPO.Ab titres was confined to those who had thyroid volumes within the intermediate range (10.1-18.8 mL) and did not further enhance the good outcome recorded when volumes were < or = 10.0 mL or > 18.8 mL. Multivariate survival analysis showed that both TPO.Ab and thyroid volume were independently associated with prognosis in breast carcinoma and that RRs for disease-free survival were of a similar order of magnitude to well-established prognostic indices such as axillary nodal status or tumor size. These findings supply evidence that manifestations of thyroid autoimmunity are associated with a beneficial effect on disease outcome in breast carcinoma and provide the strongest evidence to date of a biological link between breast carcinoma and thyroid disease.