The study presented here supports the notion that (A) the IGF-IR signaling axis is active and mediates malignant phenotypes in brain-seeking breast cancer cells, (B) both genetic and pharmacological inhibition IGF-IR decrease the malignancy of brain-seeking cells in vitro, and remarkably (C) IGF-IR shRNA-expressing breast cancer cells have a decreased ability to form brain tumors in a model of experimental brain metastasis. Here, IGF1R is linked to breast cancer.