Every organ in the adult mammalian body harbours a rare population of stem cells. Most tumours arise from the transformation of a single stem cell into a cancer stem cell that has the innate capacity to perpetuate through self-renewal, and to generate mature neoplastic cells of a particular tissue through differentiation in vivo. C0133, a 120kOa transmembrane spanning glycoprotein, was the first in a class of novel pentaspan membrane proteins to be identified in both humans and mice, and was originally characterised as a possible marker of cancer stem cells in the haematopoietic system. Since its first discovery, C0133, independently or in combination with other stem cells markers, has been identified in a variety of human tumours including prostate tumours, breast cancers, colon carcinomas, lung cancers, and brain tumours. However, the belief that C0133 may act as a universal marker of cancer stem cells has been met with a high degree of controversy in the neuro-oncology research community as the precise biological role of C0133 has yet to be established. In vivo, glioblastoma multiforme contains poorly vascularised areas associated with decreasing oxygen tension (hypoxia), recently correlated with poor patient prognosis. In this study, a direct link between decreasing oxygen tension and C0133 expression was established. Furthermore, the in vitro hypoxic micro-environment appeared to facilitate a role in the biological behaviour of the glioma, as well as upregulating the CD133 phenotype. Distinct biological differences were also obvious between the CD133+ve and CD133"ve cell fractions; the CD133 protein appeared to not facilitate a role in cellular adhesion; the C0133"ve cell fraction displayed an increased invasive propensity in comparison to the C0133+ve cells; the II CD133+ve cells did not evoke cellular invasion, instead this cell fraction may be inversely linked to this biological process. Whether the CD133 protein precisely defines cancer stem cells within neoplastic glia remains to be clarified. However, this study has made significant progress towards identifying the functional role of CD133.