(EGFR) is considered a poor prognostic marker, and recent clinical data showed that treatment of metastatic triple-negative breast cancer (TNBC) with an anti-EGFR antibody improved disease control, suggesting that EGFR is an important target in TNBC. However, the biological role of the EGFR pathway in TNBC has not been well elucidated. We hypothesize that activation of the EGFR pathway induces TNBC tumorigenesis and metastasis. Our objective is to define the phenotypic characteristics of EGFR-overexpressing TNBC by establishing a genetically engineered mouse model that resembles human EGFR-overexpressing TNBC. We have induced TNBC tumors in mice by a novel in vitro oncogene-introduction system. Mutant H-RAS was transfected into mouse mammary epithelial cells (MECs) with knockout of the tumor suppressor Ink4a/Arf. The transfected MECs were inoculated into mouse mammary fat pads. The resulting tumors resembled human TNBC in their pathological and molecular findings. However, H-RAS overexpression or mutation is not a common finding in human TNBC.