In our haste to fi nd and eliminate breast cancer stem cells, it appears as though we may have missed something. Contrary to current thought, a recent paper by Meyer and colleagues demonstrates developmental plasticity of breast cancer cells with respect to the CD24 cell surface marker, such that CD44(pos);CD24(pos) and CD44(pos);CD24(low/-) cells are able to give rise to one another in an activin/nodal-dependent manner, and that cells derived from single cells of either phenotype are capable of forming tumors as xenografts. If confirmed clinically, these data imply that simply targeting the CD44(pos);CD24(low/-) breast cancer stem cell for breast cancer treatment may be destined to fail unless this plasticity is taken into account and prevented.