Purpose: To determine whether [F-18]-fluorodeoxy-D-glucose ([F-18]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. Patients and Methods: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [F-18]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. Results: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P = .037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of; chemotherapy was significantly greater in lesions that achieved a partial (P = .013), complete macroscopic (P = .003), or complete microscopic (P = .001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and ct specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P = .076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P = .037). The mean change in DUR and K after the first pulse of chemotherapy war significantly greater in responding lesions [DUR, P = .038; K, P = .012). Conclusion: [F-18]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response. J Clin Oncol 18:1676-1688, (C) 2000 by American Society of Clinical Oncology.