In the present study, we report that cholesterol content modulates the rigidity and fluidity of plasma membranes to maintain the surface levels of ErbB2 in breast cancer cells, while the reduction in cholesterol abundance in plasma membrane facilitates the endocytic degradation of ErbB2 and thus synergizes with the tyrosine kinase inhibitors against ErbB2 to suppress ErbB2-positive breast cancer growth. The gene discussed is ERBB2; the disease is breast carcinoma.