Antibodies reacting with the host protein p53 were found in the sera of patients with primary or secondary carcinoma of the breast. Fourteen out of the 155 sera from breast cancer patients tested were positive for anti-p53 antibodies (9%) and no positives were detected among 164 control sera from normal women tested. The locations of the first metastasis in patients with positive sera were unusual, with more lung metastases and fewer bone metastases than expected. The detection of anti-p53 antibodies indicates that p53 is altered in amount, type or presentation in breast tumors so that it becomes immunogenic.