A promising new option as the treatment of choice for premenopausal patients with metastatic breast cancer (MBC) could be the combination of a luteinising hormone-releasing hormone analog and an aromatase inhibitor. Very little data about the use of goserelin with anastrozole in advanced breast cancer are available, and no cohort studies on the efficacy of goserelin with letrozole in advanced premenopausal breast cancer patients have been reported. We present the single-centre, retrospective, experience of goserelin plus letrozole in a total of 52 premenopausal women with MBC. All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks along with letrozole 2.5 mg daily as first-line (n=36) and second-line (n=16) hormonal treatment. The median duration of goserelin with letrozole treatment was 11 (range, 2-61) months, and the median duration of overall follow-up was 31 (range, 3-66) months. The objective response rate (ORR) was 21.1%, with two complete response (CR) (3.8%) and nine partial response (PR) (17.3%). Stable disease (SD) lasting more than 6 months was achieved by 26 patients (50.0%). Thus, goserelin with letrozole conferred clinical benefit (CB) in 37 women (71.1%). The progression-free survival (PFS) was 10 months. CR was exclusively observed in hormone receptor-double-positive patients. Drug therapy was well tolerated; no grade 3/4 toxicities were reported. Goserelin plus letrozole appears to be an efficacious and well-tolerated regimen in women with advanced breast cancer. Further prospectively randomized studies involving more patients and longer follow-up are indicated.