This multicenter phase II trial evaluated the efficacy and tolerability of 4 months of neoadjuvant exemestane in 44 postmenopausal patients with estrogen receptor (ER)-positive and/or progesterone receptor-positive, stage II to IIIB breast cancer measuring >or=3 cm. Pathological response was assessed by a central review board using response criteria proposed by the Japanese Breast Cancer Society. Clinical response [complete or partial response (PR)] was assessed by caliper, mammography, or ultrasound. Rates of breast-conserving surgery (BCS) and adverse events were also evaluated. A pathological response was observed in 13 (43%) of 30 patients who underwent surgery at 4 months. Fourteen patients were excluded from the pathological analysis: eight continued exemestane because of PR or stable disease (SD) at 4 months, three underwent chemotherapy because of progressive disease, and three underwent surgery within 2 months because of adverse events. A clinical response was seen in 27 (66%) of 41 evaluable patients. BCS was performed in 27 (90%) of 30 patients who underwent surgery at 4 months. Of the ten patients eligible for mastectomy at baseline, six chose to continue exemestane treatment without surgery because of a PR or SD at 4 months. Adverse events, most of which were grade 1, occurred in <or=10% of patients. These results suggest that neoadjuvant exemestane treatment is effective and well tolerated in postmenopausal women with ER-positive breast cancer. Further studies are required to determine the optimal duration of neoadjuvant treatment and to identify response criteria that can more accurately predict long-term outcomes.