Abstract Background: Mammographic density (MD), a strong marker of breast cancer risk, is influenced by genetic, environmental, and hormonal factors. Cadmium, a persistent and widespread environmental pollutant, has been associated with risk of breast cancer, and laboratory evidence suggests cadmium is a carcinogen in the breast. Urinary cadmium concentration is a measure of exposure to cadmium over a prior 20-30 years. Methods: In a cross-sectional study of MD and urinary cadmium concentration, percentage MD (MD%) and Breast Imaging-Reporting and Data Systems (BI-RADS) density category were determined from screening mammograms of 190 premenopausal women ages 40-45 years recruited from a breast cancer screening program at a large integrated healthcare system. Women completed a health questionnaire, and the cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and corrected for urine creatinine. Multivariable linear regression and logistic regression were used to estimate the strength of association between urinary cadmium and mammographic breast density, adjusted for age, parity, smoking history, race, and body mass index. Results: Adjusted mean MD% among women in the upper tertile of creatinine-corrected urine cadmium was 4.6% higher (95% confidence interval (CI): −2.3 to 11.6%) than in women in the lowest cadmium tertile. Each twofold increase in urine cadmium was associated with higher odds of MD% in the upper tertile (odds ratio (OR): 1.29, 95% CI: 0.82-2.02) or a BIRADS category rating of “extremely dense” (OR: 1.75, 95% CI: 1.14-2.70). Conclusions: Exposure to cadmium may be associated with increased breast density in premenopausal women. These results support earlier findings that cadmium may increase risk of breast cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A3.