Introduction: Our objective was to determine whether serum leptin levels and obesity-related factors could affect outcome for metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). Methods: Sixty MBC patients treated with first line hormonal therapy were enrolled in this study. Results: Median age was 51 years (range 28-75). Median leptin level was 19400 pg/ml (1970-91900) and estradiol level 29.6 pg/ml (4.0-181.9). Factors associated with overall survival in univariate analysis were age and waist-to-hip ratio (WHR), whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognostic marker only if the leptin level was ≥19400 pg/ml (HR = 0.38; 95% CI: 0.16-0.91). Conclusions: This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in MBC patients treated with AIs. © 2011 The Japanese Breast Cancer Society.