A set of markers for cancer stem cells are provided. The cells can be prospectively isolated or identified from primary tumor samples, and possess the unique properties of cancer stem cells in functional assays for tumor initiation, cancer stem cell self-renewal and differentiation. In addition, cancer stem cells can be used as a predictor for disease progression. The CSC have the phenotype of being positive for expression of CD133, and for EGFRvIII. In another embodiment of the invention, compositions are provided of a bispecific reagent that recognizes CD133 and EGFRvIII, including bispecific antibodies, which are optionally conjugated to a detectable marker, chemotherapeutic agent are radionuclide for imaging or therapy.