Metastatic breast cancer is an incurable disease even with high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (ASCT). Even though phase III studies have not shown a survival advantage for this group as a whole, it is possible that a small subset of patients may benefit from HDC/ASCT with careful patient selection. A total of 198 patients from three different institutions were treated with HDC/ASCT. After complete staging, patients with central nervous system or bone marrow involvement were excluded. The HDC regimen consisted of: Carboplatin 600 mg/m(2) IV infusion over 48 hours, Thiotepa 300 mg/m(2) IV infusion over 2 hours, and Cytoxan 60 mg/kg IV infusion given over 2 hours x3 days. The median age at the time of transplant was 46 (24-62) years and median follow-up was 20 months. Hormone receptor status was known in 148 patients, of whom 84 had estrogen receptor (ER) and/or progestrone receptor (PgR)-positive tumors. Eighty patients had no evidence of disease at the time of HDC/ASCT (CR1). At the completion of HDC and ASCT, complete responses (CR) were seen in an additional 57 patients (CR2). Using Kaplan-Meier analysis, the median relapse-free survival (RFS) for the entire group was 15 months and overall survival (OS) was 27 months. The patients in CR1 had a median RFS and OS of 20.7 and 50.6 months, respectively. This was very similar to the RFS and OS in patients achieving CR2 after HDC/ASCT (p < 0.001; median: 19 and 40 months, respectively). In contrast, the patients with persistent residual disease had an RFS and OS of 7 and 12 months (p < 0.001). These data show that patients achieving a CR after HDC/ASCT have a better relapse-free and OS, when compared to patients with persistent residual disease after HDC/ASCT. This study suggests that a subset of patients with residual metastatic breast cancer after standard chemotherapy can achieve CR with HDC and ASCT which may result in better long-term outcome.