| Cancer stem cells (CSCs) drive tumor initiation and metastasis in several types ofhuman cancer. However, the contribution of ovarian CSCs to peritoneal metasta-sis remains unresolved. The cell adhesion molecule CD44 has been identi?ed as amajor marker for CSCs in solid tumors, including epithelial ovarian cancer. CD44exists as a standard form (CD44s) and also as numerous variant isoforms (CD44v)generated by alternative mRNA splicing. Here we show that disseminated ovariantumors in the pelvic peritoneum contain highly enriched CD44v6-positive cancercells, which drive tumor metastasis and are responsible for tumor resistance tochemotherapy. Clinically, an increased number of CD44v6-positive cancer cells inprimary tumors was associated with a shortened overall survival in stage III–IVovarian cancer patients. Furthermore, a subpopulation of CD44v6-positive cancercells manifested the ability to initiate tumor metastasis in the pelvic peritoneumin an in vivo mouse model, suggesting that CD44v6-positive cells show thepotential to serve as metastasis-initiating cells. Thus, the peritoneal disseminatedmetastasis of epithelial ovarian cancer is initiated by the CD44v6-positive subpop-ulation, and CD44v6 expression is a biomarker for the clinical outcome ofadvanced ovarian cancer patients. Given that a distinct subpopulation of CD44v6-positive cancer cells plays a critical role in peritoneal metastasis, de?nitive treatment should target this subpopulation of CD44v6-positive cells in epithelialovarian cancer |