We provide experimental evidence that the rare subgroup of triple-negative breast cancer characterized by constitutive activation of the NOTCH1 signaling pathway is sensitive to the anti-tumor action of all-trans retinoic acid, the active metabolite of vitamin A. In this tumor context, all-trans retinoic acid exerts not only an effective action on its own, but it also stimulates the inhibitory activity of γ-secretase inhibitors, a series of therapeutic agents targeting NOTCH1, on cancer cell growth. Here, NOTCH1 is linked to triple-negative breast carcinoma.