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BACKGROUND. Early diagnosis of recurrent breast cancer is crucial to selection of the most appropriate therapy. The current study evaluated the role of FDG‐PET/CT in the assessment of suspected recurrent breast cancer in patients who presented with elevated serum tumor markers. METHODS. Forty‐seven consecutive FDG‐PET/CT studies of 46 women (aged 32–79 years; mean, 59.9 years) with a history of breast cancer presented with elevated serum tumor markers 1–21 years (mean = 6.2 years) after their initial diagnosis and were retrospectively evaluated. PET/CT results were confirmed by pathology (n = 11), further imaging, and follow‐up (mean = 17.2 months; n = 36). Changes in further management based on PET/CT were recorded. RESULTS. Thirty (65%) patients had tumor recurrence, and 16 (35%) patients showed no further evidence of disease. Thirty‐one patients had 32 abnormal PET/CT studies, and 15 patients had normal studies with an overall sensitivity, specificity, and accuracy of 90%, 71%, and 83%, respectively. In 37 patients, PET/CT was compared with contrast‐enhanced CT and had a higher sensitivity (85% vs 70%), specificity (76% vs 47%), and accuracy (81% vs 59%). PET/CT had an impact on the management of 24 (5l%) patients. Of these, chemotherapy or radiotherapy was started in 16 patients, treatment was modified in 2 patients, and 6 patients were referred to biopsy, followed by referral to surgery for 2 patients. CONCLUSIONS. In patients with breast cancer and rising tumor markers, FDG‐PET/CT had high performance indices and was superior to CT for diagnosis of tumor recurrence, which led to changes in the subsequent clinical management of 51% of these patients. Cancer 2006. © 2006 American Cancer Society.