Mutations in the p53 tumor suppressor gene are the most common genetic alterations associated with malignant tumors including breast and gynecologic carcinomas. Overexpression of p53 protein is a result of increased protein stability caused through conformationally alteration. Accumulation of mutant p53 in tumor cells may lead to a humoral immune response with development of p53 autoantibodies. In the present study we investigated the sera of 72 patients undergoing surgery for primary breast cancer and the relation between p53 antibody production, prognostic parameters and clinical outcome. Circulating p53 antibodies were detected in 15 of the 72 examined patients (21%). A correlation to conventional prognostic factors was not observed. Yet the overall survival was worse in patients with p53 antibodies (p < 0.04), suggesting a more aggressive tumor type.