Pigment epithelium-derived factor (PEDF) is a cytokine that is expressed in human primary breast cancers but not in breast cancer brain metastases. Patricia Steeg and colleagues now show that human and mouse breast cancer cells expressing PEDF cannot establish large brain metastases. In addition, the neurons that surrounded the PEDF-expressing metastases that did form were less likely to die as a result of the damage induced by the growing metastases. Therefore, PEDF seems to both limit breast cancer cell growth and be neuroprotective.