The anti-tumor function of STAT1 through its capacity to control the immune system and promote tumor immune surveillance has been well understood. However, little is known about cell autonomous (i.e., tumor cell-specific) functions of STAT1 in tumor formation. Recent studies have provided strong evidence that STAT1 suppresses mouse mammary gland tumorigenesis by both, immune regulatory and tumor cell-specific functions of STAT1. Specifically, STAT1 deficiency in the mouse mammary gland inhibits ErbB2/Neu-mediated tumorigenesis and contributes to spontaneous formation of estrogen receptor α (ER α)-positive as well as ER α-negative tumors closely resembling human disease. Herein, we review the anti-tumor functions of STAT1 revealed from investigations of murine breast cancer models and from characterization of the signaling properties of STAT1 in human breast tumor cells. The significance of STAT1 in breast cancer is underscored by studies proposing a prognostic value for the expression and/or phosphorylation of STAT1 for specific molecular types of breast cancer. Furthermore, STAT1 dependent transcription is proposed to contribute to therapeutic responses by modulating the efficacy of chemotherapeutic drugs and the development of drug resistance.