Using an engineered metastatic niche, we identified a 9‐gene signature (Dhx9, Dusp12, Fhl1, Ifitm1, Ndufs1, Pja2, Slc1a3, Soga1, Spon2) that successfully delineated metastatic breast cancer from nonmetastatic breast cancers including an invasive cell line without metastatic potential. Here, MTCL2 is linked to breast carcinoma.