Studies in breast cancer patients have shown that tamoxifen decreases circulating levels of lipoprotein(a) (Lp(a)), an independent risk factor for premature coronary heart disease, and insulin-like growth factor-I (IGF-I), a promising surrogate biomarker for breast cancer. Since a common hormone regulatory pathway has been suggested for both biomarkers, we measured Lp(a) levels for 6 months in 68 healthy women participating in a chemoprevention trial of tamoxifen and correlated its changes with IGF-I. After 1 month, mean Lp(a) levels decreased by 23% with tamoxifen and increased by 6% with placebo (P = 0.033). No further change was observed after 2 and 6 months. Women with abnormal values at baseline (i.e. > 30 mg/dl) showed the highest reduction. The mean levels of IGF-I decreased by 23.5% with tamoxifen and remained stable with placebo, but the changes induced by tamoxifen in Lp(a) and IGF-I levels were uncorrelated. Our results support the observation that tamoxifen may be a suitable preventive option for women with multiple disease risk factors.