Use of chemoprevention to prevent development of breast cancer among high-risk women has been limited despite clinical evidence of its benefit. Our goals were to determine whether knowledge of the benefits and risks of tamoxifen affects a woman's willingness to take it to prevent breast cancer, to define factors associated with willingness to take tamoxifen, and to evaluate race/ethnic differences. Women, ages 50-80, who identified as African American, Asian, Latina, or White, and who had at least one visit to a primary care physician in the previous 2 years, were recruited from ambulatory practices. After a screening telephone survey, women completed an in-person interview in their preferred language. Multivariate regression models were constructed to examine the associations of demographic characteristics, numeracy, breast cancer history, and health knowledge with willingness to take tamoxifen. Over 40% of the women reported they would likely take tamoxifen if determined to be at high risk, and 31% would be somewhat likely to do so. Asian women, those with no insurance, and those with less than high school education were significantly more likely to be willing to take tamoxifen. Higher scores on numeracy and on breast cancer knowledge were also associated with willingness to take tamoxifen. A higher tamoxifen knowledge score was inversely related to willingness to take the drug. Factors affecting women's willingness to take breast cancer chemoprevention drugs vary and are not determined solely by knowledge of risk/benefit or risk perception.