Cancer cells exhibit altered metabolism including high demand for cholesterol for rapid cell proliferation. Scavenger receptor BI (SR-BI) is a HDL receptor. It mediates the uptake of cholesterol from HDL. Recent studies including ours indicate that SR-BI is highly expressed in breast cancer and the levels of SR-BI expression are negatively correlated with cancer survival. We hypothesize that SR-BI-mediated cholesterol uptake from HDL provides cholesterol for cancer cell growth, and blocking SR-BI-mediated cholesterol uptake from HDL inhibits cancer cell proliferation, which may provide a novel approach for cancer therapy. We currently use a combination of molecular, cellular and genetically manipulated animal models to test our hypothesis.