Definition of the malignant transformation event is central to a distinction between neural stem cells and cancer stem cells. In such manner, the descriptive analysis of various tumors such as gliomas would allow for the distinction of genetic injury and probably epigenetic events that transform gene transcription pathways. Hypoxia is a major conditioning influence acting on stem cell niche microenvironments that evolve in terms particularly of micro-vascular dynamics. The incremental involvement of entire fields of cancerization allows for the establishment of permissive conditions of repetitive nature and within the contextual involvement of multiple clones of injured cells that condition, in turn, the stem cell niche. In view of the establishment of progressive malignant change, it is significant to view the cancerization as an integral involvement of both sequential and concurrent events in defining the roles of stem cells and cancer stem cells in terms of a primal process of dedifferentiation beyond simple markers of morphologic transformation.