Abstract Background/Aims: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin use and risk for breast cancer, stratified by HR status. We conducted a large case-control study within Kaiser Permanente of Northern California (KPNC) to determine whether chronic use of lipophilic statins is associated with decreased risk of HR-negative breast cancer or other breast cancer subtypes. Methods: We identified 22,488 breast cancer cases diagnosed from 1997 to 2007, and 224,860 controls matched to cases based upon birth year and duration of KPNC pharmacy coverage. Use of lipophilic statins was ascertained using the comprehensive electronic pharmacy records of KPNC. Results: We found no association between lipophilic statin use (≥2 y versus never) and overall breast cancer risk (odds ratioadj, 1.02; 95% CI, 0.97-1.08) in conditional logistic regression models adjusted for oral contraceptive and hormone therapy use. Women who used lipophilic statins did not have a decreased risk of HR-negative breast cancer (odds ratioadj, 0.98; 95% CI, 0.84-1.14) nor altered risk of HR-positive disease (odds ratioadj, 1.03; 95% CI, 0.97-1.10). Furthermore, lipophilic statin use was not associated with risk of any of the intrinsic subtypes, luminal A, luminal B, human epidermal growth factor receptor 2 positive/estrogen receptor negative, or triple negative. Conclusions: Our results do not support an association of lipophilic statin use with the risk for breast cancer in general or with risks of HR-negative or other breast cancer subtypes specifically. Impact: These findings do not confirm previous reports of a possible preventive association. Cancer Epidemiol Biomarkers Prev; 19(10); 2479–87. ©2010 AACR.