In the collaboration with Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University, Fukusumi et al. found CD10 as a novel marker of therapeutic resistance and cancer stem cells in head and neck squamous cell carcinoma. By studying three HNSCC cell lines (FaDu, Detroit562, and BICR6), treated with cisplatin or radiation, cell surface antigens were analysed by LyoPlateTM, a novel cell surface antigen array. The expression levels of antigens highly expressed after treatments were further compared between cisplatin-resistant Detroit562 cells and its parental line. Association of the candidate antigen with CSCs properties, namely sphere formation and in vivo tumourigenicity, was also examined. The result indicated that CD10, CD15s, CD146, and CD282 were up-regulated across the treated cell lines, while the increased expression of CD10 was prominent in the cisplatin-resistant cell line. FACS-mediated isolation revealed that the CD10-positive subpopulation was more refractory to cisplatin, fluorouracil, and radiation than the CD10-negative subpopulation. It also showed an increased ability to form spheres in vitro and tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC marker OCT3/4 at a higher level than that in the CD10-negative subpopulation. Thus CD10 is associated with therapeutic resistance and CSC-like properties of HNSCC. CD10 may serve as a target molecule in the treatment of refractory head and neck squamous cell carcinoma (HNSCC).