Exemestane is a potent steroidal aromatase inhibitor (AI) with activity in post-menopausal women with metastatic breast cancer, with a reported clinical benefit (CB) rate of 24.3% after prior AI therapy. Data on 114 patients (112 female, 2 male) were obtained retrospectively at two cancer centres. Sixty-five percent of patients were confirmed as oestrogen receptor (ER) positive. All patients had received prior third-generation AI therapy. Responses were seen in 5% and the overall CB rate (CR+PR+SD24 weeks) was 46%. Median PFS and OS were 18 and 61 weeks, respectively. In patients with visceral disease, the CBR was 33%. Patients with known ER-positive disease had a CBR of 47%, and a median TTP of 19 weeks. No benefit was seen in patients with known ER-negative disease. Survival was better in those with CB (median survival not reached in those with CB, 28 weeks in those without CB P<0.0001). Efficacy persisted in those patients who had received 3 prior lines of hormonal therapy, including adjuvant treatment. These data confirm exemestane to be an effective therapy after third-generation non-steroidal AI in post-menopausal ER-positive metastatic breast cancer, including visceral disease.