It is thought that squamous lung cancer arises in a stepwise fashion from normal stem cells to premalignant lesions to invasive lung cancer. This study used a special technique to isolate stem cells and cells of premalignant lesions from the airways of patients with squamous lung cancer. It was also used to remove tumor cells from the same patient tissues. Studies of the gene expression profiles of these sets of samples from individual patients were analyzed to determine which pathways were turned on or off in stem cells of the airway as compared to premalignant lesions and squamous lung cancer. Some of the interesting pathways found involve cell metabolism which was found to be altered in the cells of the premalignant lesions and further altered in the tumor cells. Some pathways associated with oncogenes were predicted to be activated in the premalignant lesions although the gene expression levels were not different and similarly tumor suppressor gene pathways were predicted to be down regulated in the cells of premalignant lesions. This study begins to shed some light on the stepwise progression of squamous lung cancer and provides the first resource of gene expression data for the research community.