Cytoreductive surgery followed by platinum/taxane results in complete response in 70&percent; of ovarian cancer patients, but most patients will relapse with drug-resistant disease within 18 months. An emerging model for the development of drug-resistant tumors invokes a pool of self-renewing malignant progenitors known as cancer-initiating cells. Zhang and colleagues identify and characterize a subpopulation of ovarian cancer–initiating cells (OCICs) capable of serial propagation of their original tumor phenotype in animals. Stemness properties of OCICs include enhanced chemoresistance to cisplatin or paclitaxel and upregulation of stem cell markers Bmi-1, stem cell factor, Notch-1, Nanog, nestin, ABCG2, and Oct-4. To identify an OCIC cell surface phenotype, immunostaining showed significant up-regulation of the hyaluronate acid receptor CD44 and stem cell factor receptor CD117, a tyrosine kinase oncoprotein. Isolated CD44⁺CD117⁺ cells could also serially propagate theiroriginal tumor phenotype in animals. These findings suggest that epithelial ovarian cancers derive from a subpopulation of CD44⁺CD117⁺ cells, thus representing a possible therapeutic target for this devastating disease. For details, see the article by Zhang et al. on page 4311 of this issue.