Purpose: To identify the prognostic value of biological markers at initial operation for metastatic breast cancer, we measured the presence of estrogen receptor-alpha (ERα), progesterone receptor (PgR) and human epidermal growth factor receptor type 2 (HER2),and histological grade (HG) of tumors. Methods: One-hundred and seventy-six patients, aged 29 to 90 (median: 51 years), with recurrent breast cancer underwent primary operation at our department during the period from 1983 to 2000. Clinicopathological factors examined at primary operation included menopausal symptoms, presence of axillary lymph node metastasis, tumor size, HG, HER2, ERα and PgR.Factors examined at recurrence included site of primary recurrence, disease-free interval(DFI) and tumor markers, such as CEA and CA15-3. The relationship between these factors and prognosis following recurrence was assessed. Results: Menopausal status, axillary lymph node metastasis and tumor size at primary operation had no significant effect on prognosis. Patients with low HG, positive expession of ERα and PgR, and low HER2 expression had a good prognosis, similar to those with long DFI and distant metastases. After distant metastases, HER2 was found to be the most important prognostic factor following recurrence and in predicting response to drug therapy.Conclusion: Biological factors indicating tumor malignancy at the time of the first operation are also important prognostic factors following tumor recurrence.