To shed light on the engagement of CD44/CD44v6 in CIC activities, we will first introduce the CD44 molecule, CIC and exosomes (Exo) and then outline the state of knowledge on the linkage between CD44/CD44v6 and CIC with emphasis on the requirement of a niche (Prasetyanti et al., 2013), apoptosis resistance (Ramdass et al., 2013; Colak and Medema, 2014; Vlashi and Pajonk, 2015), epithelial mesenchymal transition (EMT) (Dontu and Wicha, 2005; Wells et al., 2011) and tumor progression (Elshamy and Duhé, 2013). The gene discussed is CD44; the disease is neoplasm.