CD36 is a trans-membrane receptor that regulates apoptosis and angiogenesis in response to its ligand thrombospondin-1 (TSP-1). This study measures expression of CD36 and TSP-1 in breast cancer cell lines. Expression of TSP-1 was approximately 50-fold higher in the aggressive cell line MDA-MB-231 than in less aggressive MCF-7, BT-474, ZR-75 and T47-D cells. In contrast, MDA-MB-231 express 30 to 100-fold less CD36 than less aggressive cells. Hormone-dependent T47-D and MCF-7 cells down-regulate CD36 in response to estradiol, and anti-hormone ICI 182,780 block this effect. These results suggest that the estrogen receptors play a role in regulating CD36 expression and ICI 182,780 prevents loss of CD36 as a novel mechanism for its anti-estrogen effect in breast cancer cells.