Hypercholesterolemia is clinically linked to breast cancer progression. Starting from our results published on Nature Communications, the focus of this review is to briefly summarise the recent findings in the field and discuss how metabolic reprogramming is definitely connected to endogenous cholesterol biosynthesis. We examine how enhanced metabolism promotes invasiveness and cancer growth. In particular, we explain how this mechanism of resistance is specifically associated with aromatase inhibitors treatment. Finally, we review how the field is now considering the development of anti cholesterol therapeutics and biomarkers to stratify and treat primary and secondary breast cancer patients.