The aim of this study was to study the effectiveness of the Swenerton score in assessing extent of disease as an independent prognostic and predictive factor in patients with metastatic breast cancer (MBC) who receive high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplant (AHSCT). Two-hundred thirty-two patients with MBC underwent HDCT. Extent of disease was assessed quantitatively using the Swenerton score. A retrospective analysis was performed using Cox proportional hazards regression and logistic regression models. One hundred three (44%) patients had a complete response (CR) after HDCT. Bone marrow as source of hematopoietic stem cells, hormone-receptor-negative status, and visceral involvement correlated with both worse overall survival (OS) and progression-free survival (PFS). Short disease-free interval, multiple sites of metastatic disease, and less than 50% reduction in the Swenerton Score during induction chemotherapy correlated with worse OS. Patients in CR at the time of HDCT had better PFS than patients in partial response, stable disease, or progressive disease. Fifty-six patients who underwent conversion to CR after HDCT had a similar median OS (not reached v 74 months; P =.51) and PFS duration (22 v 44 months; P =.15) as patients who received HDCT after a CR to standard-dose chemotherapy (SDCT). Conversion to CR was predicted by a >/=50% reduction in the Swenerton score during SDCT (odds ratio [OR] 3.32, P <.01) and soft-tissue disease (OR 4.08, P <.01). The presence of multiple metastatic sites predicted decreased probability of conversion to CR (OR 0.34, P <.01). The Swenerton score provides a thorough estimate of disease extent, and reduction of Swenerton score by SDCT is potentially useful for selecting the optimal candidates for HDCT trials who may achieve long-term disease control.