High-density lipoprotein cholesterol (HDL-C) has been suggested to be associated with breast cancer. However, the roles of HDL-C and hypertriglyceridemia on breast cancer still have been controversial. The goal of this study was to investigate the association between HDL-C with breast cancer risk, stratifying by menopausal status, and body mass index. The hormonal receptor status of breast has been proposed to modify the effect of HDL-C on breast cancer. Multicenter hospital-based case-control study was conducted from November 2004 to December 2005 in Korea. After one to two individual matchings by age (+/-5 years) and menopausal status, 690 cases and 1,380 controls were included in the analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by conditional, unconditional, and multinomial logistic regressions. Protective effect of HDL-C on breast cancer was only observed among premenopausal women with an OR (95% CI) of 0.49 (0.33-0.72) for HDL-C > or = 60 versus <50 mg/dL (P(trend) < 0.01). Only nonobese premenopausal women had a significant decreased risk (OR, 0.34; 95% CI, 0.22-0.53). OR (95% CI) of low HDL-C (<50 mg/dL) and high triglyceride (TG; > or = 150 mg/dL) category was 2.20 (1.32-3.67) on estrogen receptor-negative and progesterone receptor-negative breast cancer compared with high HDL-C (> or = 50 mg/dL) and low TG (<150 mg/dL) category. This study suggests that higher level of HDL-C may reduce breast cancer risk among premenopausal women. Estrogen receptor-negative and progesterone receptor-negative breast cancer was associated with dyslipidemia, which implicates that association among HDL-C, TG, and breast cancer may be modified by receptor status.