BACKGROUND: The aim of this study was to investigate the predictive value of early changes in (18)F‐fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)‐positive metastatic breast cancer. MATERIALS AND METHODS: Patients underwent (18)F‐FES PET/CT scans at both baseline (scan 1) and day 28 (scan 2). The maximum standardized uptake value (SUVmax) of all metastatic sites was determined in each scan, and the percentage reduction in SUVmax (ΔSUVmax) was calculated as [(SUVmax on scan 1‐SUVmax on scan 2)/ SUVmax on scan 1] * 100%. RESULTS: In total, 294 (18)F‐FES‐positive lesions from 36 patients were identified. The (18)F‐FES SUVmax varied widely among lesions (median 5.7; range 1.8–32.4) and patients (median 5.1; range 2.5–13.2). After treatment, the median SUVmax among lesions and patients was 2.1 and 2.1, respectively. The ΔSUVmax ranged from −5.1% to 100%, with a median reduction of 61.3%. Using receiver operating characteristic analysis, the optimal cutoff point to discriminate patients who could derive clinical benefit from fulvestrant was determined to be 38.0%. Patients with a median ΔSUVmax ≥38.0% experienced significantly longer progression‐free survival (PFS) than those with ΔSUVmax