Leptin plays an important role in the regulation of body fat homeostasis, and potential associations of leptin receptor gene (LEPR) polymorphisms with obesity have been suggested. Obesity is considered to relate to breast cancer. We assessed the role of leptin in relation to breast cancer. We measured the serum leptin concentrations of 45 Korean pre-treatment patients with breast cancer and 45 age-matched controls. By direct sequencing, we investigated four leptin receptor gene (LEPR) polymorphisms at codons 109, 223, 656, and 1019. There was no significant difference between the mean leptin concentrations of the patient and control groups in both pre- and post-menopausal women. The frequencies of the wild-type for LEPR codons 109, 223, and 1019 were very low. No increased risk estimate was found for the four LEPR polymorphisms. Our results indicate that it is difficult to explain breast cancer on the basis of serum leptin concentrations or polymorphisms in the LEPR gene.