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. The gene discussed is SPON2; the disease is breast carcinoma.