This study identifies and characterizes a rare population of CD133+ cancer stem-like cells in lung cancer. These cells, which are undifferentiated and express CD133, can grow indefinitely as tumor spheres in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. Injection of 10^4 CD133+ cells into immunocompromised mice generated tumor xenografts that phenotypically matched the original tumors. Upon differentiation, these cells acquired lineage-specific markers but lost their tumorigenic potential and CD133 expression. The study also found that lung cancer spheres are resistant to conventional chemotherapy, suggesting that they may be responsible for the poor therapeutic response observed in lung cancer patients. These findings highlight the importance of targeting the tumorigenic population of lung cancer stem cells for more effective therapies.This study identifies and characterizes a rare population of CD133+ cancer stem-like cells in lung cancer. These cells, which are undifferentiated and express CD133, can grow indefinitely as tumor spheres in serum-free medium containing epidermal growth factor and basic fibroblast growth factor. Injection of 10^4 CD133+ cells into immunocompromised mice generated tumor xenografts that phenotypically matched the original tumors. Upon differentiation, these cells acquired lineage-specific markers but lost their tumorigenic potential and CD133 expression. The study also found that lung cancer spheres are resistant to conventional chemotherapy, suggesting that they may be responsible for the poor therapeutic response observed in lung cancer patients. These findings highlight the importance of targeting the tumorigenic population of lung cancer stem cells for more effective therapies.