The ability to establish a prognosis for patients with early breast cancer is an important clinical issue. Recent studies have shown that antibodies to haptoglobin-related protein (Hpr) may be useful in stratifying early patients with breast cancer according to their relative risks of recurrence. Nearly 30% of early breast cancers express proteins bearing Hpr epitopes. Hpr-positive breast cancers are more likely to recur after primary resection and are associated with shorter disease-free intervals. This immunohistochemical study examines temporal changes in Hpr expression during the course of disease in 48 patients with fatal breast carcinoma. Thirty-seven primary tumors (77%) were Hpr positive. Ten of the 11 initially negative tumors (91%) were Hpr positive at the time of recurrence. In contrast, only 10 of the 37 initially positive tumors (27%) were Hpr negative with relapse. Of 18 axillary nodes that were examined, 16 (89%) were Hpr positive; all four lymph nodal metastases in patients with initially negative primary tumors were Hpr positive. The authors conclude that the acquisition of Hpr expression parallels increased malignant potential and that Hpr expression, once acquired, tends to remain a permanent characteristic of any given mammary tumor.