Leptin is a hormone with multiple biological actions which is produced predominantly by adipose tissue; in humans, plasma levels correlate with total body fat, and particularly high concentrations occur in obese women. Several actions of leptin, including the stimulation of normal and tumor cell growth, migration and invasion, and enhancement of angiogenesis, suggest that this hormone can promote an aggressive breast cancer phenotype which can be estrogen-independent. This effect may involve activation of the transcription factor NFkappaB. Leptin can also induce aromatase activity, with the potential for the promotion of estrogen production from androstenedione in adipose tissue, and hence the stimulation of estrogen-dependent breast cancer progression. On this basis, we hypothesize that leptin, perhaps in association with insulin, the plasma concentrations of which correlate with those of leptin, has an important role in the known adverse effect of obesity on breast cancer.