OBJECTIVE: To evaluate the accuracy and value of the fourth and subsequent post-therapy follow-up fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) scans in the clinical assessment of breast cancer patients. MATERIALS AND METHODS: Ninety-two female patients, with a total of 426 fourth and subsequent follow-up PET/CT scans, were retrospectively included. Patients were followed for a median of 23.7 months (range, 0.7-124.4) from the fourth follow-up PET/CT. The diagnostic accuracy of PET/CT, its impact on clinical assessment, patients' management, and survival outcome were established. RESULT: Of the 426 follow-up PET/CT scans, 264 (62%) were interpreted as positive and 162 (38%) were interpreted as negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the fourth and subsequent follow-up PET/CT scans were 97.7, 98.1, 98.8, 96.3, and 97.9%, respectively. Fourth and subsequent follow-up PET/CT were useful in excluding a tumor in 13.4% (39/292) of patients with a clinical suspicion of recurrence and identifying suspected recurrence in 10.5% (14/134) of patients without previous clinical suspicion. A change in management was noted in 6.7% (9/134) of scan times when the scans were performed without previous clinical suspicion of recurrence or therapy response and was 27.7% (81/292) when the scans were performed with clinical suspicion. Overall survival differed significantly between patients with all negative follow-up scans (n=23) and those who had at least one positive follow-up scan (n=69) (hazard ratio of 4.65, P<0.001). CONCLUSION: The fourth and subsequent PET/CT scans performed after the completion of primary treatment led to a change in management in 27.7% of patients when the scans were performed with clinical suspicion and only in 6.7% of patients when performed without clinical suspicion or context.