AIM: The purpose of the study was to assess the comparison of 18F-FDG PET/CT and CT in patients with breast cancer (BC) already treated with primary therapy, in evaluating the diagnostic and prognostic values. METHODS: We retrospectively studied 190 patients (187 women and 3 men, mean age 61±11 years) with previous BC (all stages) after surgery and other primary treatments. They underwent within three months CT and 18F-FDG PET/CT examinations for the evaluation of disease status. Disease relapse was confirmed by clinical evaluation and/or radiological findings. Survival curves of disease-free survival (DFS) and overall survival (OS) were computed using Kaplan-Meier method. Cox analysis regression was used to determine predictive factors of DFS and OS. RESULTS: Of the overall 190 patients, 82 (43%) had evidence of clinical and/or imaging disease relapse, while 108 (57%) did not. Sensitivity, specificity, negative predictive and positive predictive values for disease relapse or progression were of 89% vs. 77%, 73% vs. 53%, 90% vs. 75% and 72% vs. 55%, respectively for PET/CT and CT. DFS curves were significantly different in patients with both negative and positive PET/CT and CT (log-rank test 33.6; P<0.0001 and 12.7; P=0.003, respectively). OS curves were similar in patients with positive/negative PET/CT and CT (P=NS). By both univariate and multivariate Cox regression analysis positive PET/CT was found to be related to the disease recurrence (HR 0.18 and 0.20, both P<0.0001, respectively). CONCLUSION:PET/CT is more accurate than CT in identification of disease relapse in a large population of BC patients. In women at high-risk of recurrence, PET/CT imaging can provide the early detection of BC metastases, tailoring a proper treatment.