The present work analyzed the gene pattern profiles in 6 squamous non-small cell lung cancers (NSCLCs) versus 4 normal lung epithelial tissues by means of cDNA microarrays. In addition to cDNA microarray analyses, quantitative RT-PCR and immunohisto-chemical analyses were used to validate some of the results obtained. Our data enabled 7 genes to be selected by looking at the genes which were detected as being expressed in all the tumors and not expressed in all the normal samples, or inversely. Additionally, 19 genes were detected as being overexpressed in the tumors when compared to the normal tissue specimens. Of these 26 genes, 16 are not yet suspected of influencing NSCLC biology. These genes are involved in cell proliferation (G2 cyclin), signal transduction (SMARCC2, TM4SF3), apoptosis (CFLAR/FLIP), cell cytoskeleton (cytokeratins-14 and 16, alpha-tubulin isoform 1 and S100A10), cell adhesion (JUP), invasion (cathepsins H and O) and other biological processes (OAZ1, IGHG3, SCYA5/RANTES, beta-sarcoglycan and transcobalamin I). In conclusion, we identified a number of genes as being differentially expressed in squamous NSCLCs as compared to normal lung epithelial tissue. Some of these genes (such as those involved in invasion) could be used as new prognostic markers and others, like CFLAR/FLIP, could even constitute new therapeutic targets.