The early discrimination of clinically aggressive breast cancer from indolent disease would be clinically useful. Some human breast cancers express haptoglobin-related protein (Hpr), the HPR gene product, or a substance that shares epitopes with it. We retrospectively examined the association between the expression of Hpr and the recurrence of cancer in 70 patients with early breast cancer (Stage I or II) treated by mastectomy from 1977 through 1985, using immunohistochemical analysis of routinely processed paraffin-embedded tissue and evaluating it without knowledge of the patients' status. The expression of Hpr epitopes was associated with earlier recurrence according to life-table analysis (P less than 0.0002). Progesterone-receptor status (determined in 64 patients), tumor size, clinical stage, axillary-lymphnode status, mitotic index, and tumor necrosis also predicted recurrence, but multivariate analysis showed that Hpr-epitope expression was an independent prognostic factor. Since both Hpr status and progesterone-receptor status were independent predictors of recurrence, they could be combined to stratify the cases further: breast cancer was found to have recurred in 11 of 12 patients (92 percent) who were positive for Hpr and negative for progesterone receptors, in 5 of 11 (45 percent) who were positive for Hpr and positive for progesterone receptors, and in 9 of 41 (22 percent) who were negative for Hpr, in whom progesterone-receptor status had little effect. We conclude that Hpr-epitope expression is a clinically important predictor of the recurrence of cancer in patients with early breast cancer, especially in combination with progesterone-receptor status.