Breast cancer with metastatic disease is presently incurable. Significantly shorter survival rates are seen in premenopausal women despite usual therapies when compared to survival rates in older women. Median survival rates of 24-30 months are documented in large-scale prospective clinical trials of previously untreated women with metastatic breast cancer regardless of the protocol employed (chemotherapy, hormone therapy). High dose chemotherapy followed by autologous stem cell rescue (bone marrow or peripheral blood) is associated with significant response and possibly improved survival in chemosensitive patients with metastatic disease without visceral metastases though with significant toxicities and cost (median survival rate of 20 months). Patients with refractory disease have dismal results regardless of therapy (median survival rates of 8-9 months in a number of prospective trials with or without stem cell rescue). The use of alpha-interferon in such patients has not improved response. Whole body hyperthermia is of benefit in the presence of liver metastases although median survival rate is in the range of 12 months. New treatment approaches with curative intent are clearly required. We report fifty-nine patients with metastatic breast cancer refractory to common therapies who were treated with whole body hyperthermia (40 degrees C) with low dose chemotherapy and immunomodulation: five presented with brain metastases; 13 with multiple bone metastases; 8 with liver metastases; 10 with lung metastases; and 23 with multiple soft tissue metastases. Fifteen were premenopausal; 44 postmenopausal. Twenty-three achieved complete remission. Fourteen have been sustained with patients remaining alive from 17-80 months (median, 40 months). Nine failed after 20-40 months of being disease-free (mean, 32 months).