Objective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (V-d), MRglu/BF ratio, MRglu and its corresponding rate constants K-1 and k(3) were compared per tumor lesion before and during therapy. Results: At baseline, mean BF and MRglu varied among different tumor lesions, but mean V-d was comparable in all lesions. After one course of chemotherapy, mean MRglu decreased in all lesions. Mean BF decreased in breast and node lesions and increased in bone lesions. V-d decreased in breast and nodes, but did not change in bone lesions. The MRglu/BF ratio decreased in breast and bone lesions and increased in node lesions. In patients with multiple tumor lesions BF and MRglu response could be very heterogeneous, even within similar types of metastases. BF and MRglu increased in lesions of patients who experienced early disease progression or showed no response during clinical follow-up. Conclusion: BF and MRglu changes separately give unique information on different aspects of tumor response to chemotherapy. Changes in BF and MRglu parameters can be remarkably heterogeneous in patients with multiple lesions.