Background: Obesity is an established risk factor for postmenopausal breast cancer and also induces iron dysregulation via elevated hepcidin (hepatic peptide hormone). Hepcidin degrades ferroportin (Fp-only known iron exporter) and traps iron that enhances carcinogenesis within the cell. Breast tumors with high hepcidin and low Fp have poor prognosis. The purpose of this study was to determine if systemic hepcidin independently enhances the established obesity and postmenopausal breast cancer risk. Methods: A nested case (n=44)-control (n=44) study was conducted from an ongoing cohort on women seeking breast biopsies enrolled in a study to develop blood-based biomarkers. White postmenopausal women with incident breast cancer were matched for age and BMI to women with a non-proliferative benign lesion. Both cases and controls were stratified by obesity status (50% had a BMI > 30 & 50% < 30). Blood samples, anthropometric and other information were collected prior to biopsy. C-reactive protein, IL-6, leptin, adiponectin, estradiol, soluble transferrin receptor and hepcidin were measured using ELISA and cases and controls were compared with T-test, Wilcoxon Rank test and conditional logistic regression. Results: Hepcidin (p=0.02) along with other obesity related factors for breast cancer (inflammation (CRP, IL-6); leptin and estrogen; (all p values ≤ 0.05)) significantly differed with obesity status among the controls. Among the cases hepcidin levels were similar in obese and non-obese. Hepcidin (β=0.04; p value=0.043) was a significant independent predictor of disease (p value) status when controlled for age, leptin, family history of breast cancer, age of menarche and use of hormone replacement therapy and IL-6 in multivariable conditional logistic regression. Conclusions: Influence of obesity on hepcidin reported in premenopausal women also occurs post menopause. Hepcidin level is associated with breast cancer and may represent a novel mechanism to explain the link between obesity and breast cancer. Further study of this association is warranted.