Cancer stem cells (CSC) have been considered as the grass-root source of tumorigenesis. So far, CSCs have been demonstrated in many human cancers, including those of the breast, brain, prostate, colo-rectum, pancreas, ovary, etc. Recently, two papers published in Cancer Research, one on CSC of nasopharyngeal cancer (NPC) (2007, 67:3716-3724) and the other on CSC of lung cancer (LC) (2007, 67:4827-4833). Both groups of investigators isolated and enriched CSC from side population (SP) of cancer cell lines based on their ability to efflux fluorescent dye Hoechst 33342. SP accounted for a very small proportion of the tumor cells harvested; 2. 6% for NPC and 1.5% -6.1% for LC, while the majority was non-SP (NSP) unable to efflux the dye. ABC transporters , ABCG2 in particular, responsible for dye efflux capacity was demonstrated in NPC and LC, the expression by the latter was up-regulated. When the activity of the transporter was inhibited by either verapamil or reserpine, the SP was significantly reduced in size or disappeared. In both studies, tumor-initiating activity was demonstrated when SP cells were inoculated into NOD/SCID mice, while the inoculated NSP cells did not initiate tumor formation or several fold increase in number of NSP cells was needed. SP cells of NPC and LC were much more resistant to several chemotherapeutic agents, and SP cells of NPC were also more radio-resistant than NSP cells. The expression of human telomerase reverse transcriptase (hTERT) was elevated in SP cells of LC suggesting that there exists a reservoir of stem cells with unlimited proliferative potential for generating cancer cells. In NPC study, cytokine 19 was found highly expressed in SP but not in NSP cells. In addition to studies using cancer cell lines, small SP (0.03%-1. 12% ) was demonstrated in 16 clinical lung cancer samples. Taken together, the findings reported in the two papers provide additional support to the important role of CSC in tumorigenesis. So far, CSCs have been demonstrated in many human cancers, including those of the breast, brain, prostate, colo-rectum, pancreas, ovary, etc. Recently, two papers published in Cancer Research, one on CSC of nasopharyngeal cancer (NPC) (2007, 67: 3716-3724) and the other on CSC of lung cancer (LC) (2007, 67: 4827-4833). Both groups of investigators isolated and enriched CSC from side population (SP) of cancer cell lines based on their ability to efflux fluorescent dye Hoechst 33342. SP accounted for a very small proportion of the tumor cells harvested; 2.6% for NPC and 1.5% 6.1% for LC, while the majority was non-SP (NSP) unable to efflux the dye. ABC transporters, ABCG2 in particular, responsible for dye efflux capacity was demonstrated in NPC and LC, the expression by the latter was up-regulated. When the activity of the transporter was inhibited by either verapamil or reserpine, the SP was signif In both studies, tumor-initiating activity was demonstrated when SP cells were inoculated into NOD / SCID mice, while the inoculated NSP cells did not grow or number of NSP cells was needed. SP cells of NPC and LC were much more resistant to several chemotherapeutic agents, and SP cells of NPC were also more radio-resistant than NSP cells. The expression of human telomerase reverse transcriptase (hTERT) was elevated in SP cells of LC suggesting that there exists a reservoir of stem cells with unlimited proliferative potential for generating cancer cells. In addition to studies using cancer cell lines, small SP (0.03% -1. 12%) was demonstrated in 16 clinical lung cancer samples. Taken together, the findings reported in the two papers provide additional support to the important role of CSC in tumorigenesis.