Head and neck squamous cell carcinoma (HNSCC) is the eighth and thirteenth most common malignancy worldwide in males and females, respectively, with most malignant tumors of the upper airways. digestive tract being oral squamous cell carcinomas (OSCC) (Warnakulasuriya, 2009; Scully and Bagan, 2009; Nicole et al., 2010). The highest incidence of OSCC is found in India due to the higher preponderance of habits such as chewing tobacco, betel quid and areca nut which are the most important risk factors (Facompre et al., 2012). According to Gujarat Cancer & Research Registry, the scenario is worse in Gujarat as 53.65% of males and 15.64% of females of all cancers are found to be tobacco related cancers (TRC) (National Cancer Registry Report, 2008 ). Despite recent advances in first-line treatments, the 5-year survival rate after treatment remains disappointingly low, at approximately 15–50% over the past 3 decades (Carvalho et al., 2005; Prince and Ailles, 2008; Warnakulasuriya, 2009; McCullough et al., 2010). The resulting poor prognosis is due to a low response rate to current therapeutic strategies, advanced diagnosis, high risk of recurrence at the primary site and aggressive metastases to loco-regional lymph nodes, strongly suggestive of the need to improve diagnostic capabilities and effectiveness of the treatment. Increasing experimental evidence supports the cancer stem cell model in HNSCC, which favors a small percentage of cells with the ability to support tumor formation and growth, self-renewal, and differentiation into a tumor type and context-dependently. These CSCs have a likely role in therapy resistance, metastasis formation, and recurrence, alluding to the fact that targeted deletion of the… middle of the paper… has more tumorigenic potential than the CD44+ marker. Furthermore, the c-Met+/CD44+ combination produced tumors in 80% of cases while c-Met+/ALDH1+ showed tumor formation in 66% of cases (Sun and Wang, 2011). Therefore c-Met has been proposed as a potent marker of CSC in HNSCC, but further investigation with a larger number of samples and a comparison of c-Met+ with other markers of CSC and stemness could provide a clear representation (Sun and Wang , 2011). Populations (SP): Identification of CSCs is largely performed using the side population approach that involves deletion of Hoechst 33342. Hoechst 33342, a fluorescent DNA-binding dye, binds preferentially to AT-rich regions of cells tumors. These SPs express high levels of the ATP-binding cassette (ABC) transporter superfamily (e.g. MDR1, MRP1, ABCB5, ABCG2) that facilitates the efflux of this dye and other drugs (Zhang et al., 2009).