This study identifies and expands the tumorigenic population of lung cancer stem cells. Lung cancer is a leading cause of cancer-related mortality, with a poor prognosis. Cancer stem cells (CSCs) are rare, undifferentiated cells responsible for tumor initiation, maintenance, and spread. The study shows that CD133+ cells in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are tumorigenic and can form tumor spheres in serum-free medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (FGF). These cells can generate tumor xenografts in immunocompromised mice, indicating their tumorigenic potential. Upon differentiation, CD133+ cells lose their tumorigenic potential and lineage-specific markers. Lung cancer contains a rare population of CD133+ cancer stem-like cells that can self-renew and generate non-tumorigenic progeny. These cells express CD133 and other stem cell markers, such as BCRP1 and Oct3/4. The study also shows that CD133+ lung cancer cells are resistant to conventional chemotherapy, which may explain the poor therapeutic response in lung cancer patients. The identification and characterization of these tumorigenic cells may provide valuable insights for developing more effective therapies. The study highlights the importance of understanding the biology of lung cancer stem cells to improve treatment outcomes.This study identifies and expands the tumorigenic population of lung cancer stem cells. Lung cancer is a leading cause of cancer-related mortality, with a poor prognosis. Cancer stem cells (CSCs) are rare, undifferentiated cells responsible for tumor initiation, maintenance, and spread. The study shows that CD133+ cells in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are tumorigenic and can form tumor spheres in serum-free medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (FGF). These cells can generate tumor xenografts in immunocompromised mice, indicating their tumorigenic potential. Upon differentiation, CD133+ cells lose their tumorigenic potential and lineage-specific markers. Lung cancer contains a rare population of CD133+ cancer stem-like cells that can self-renew and generate non-tumorigenic progeny. These cells express CD133 and other stem cell markers, such as BCRP1 and Oct3/4. The study also shows that CD133+ lung cancer cells are resistant to conventional chemotherapy, which may explain the poor therapeutic response in lung cancer patients. The identification and characterization of these tumorigenic cells may provide valuable insights for developing more effective therapies. The study highlights the importance of understanding the biology of lung cancer stem cells to improve treatment outcomes.