Targeting phosphatidylserine (PS) on the surface of mammary tumor cells with Annexin V slowed tumor growth and reduced lung metastasis in a mouse model. Mice with tumors treated with Annexin V showed smaller tumor size, less lung luminescence indicating fewer metastases, decreased number of metastases on pathological examination, and fewer tumor colony forming units in lung cultures compared to untreated mice. The results support targeting tumor PS with Annexin V as a potential treatment for metastatic disease.