The paxillin gene (PXN) encodes a focal adhesion associated protein that could be involved in the progression of lung cancer through its interactions with the actin cytoskeleton and key signal transduction oncogenes. PXN mutations and PXN amplifications were recently identified in nonsmall-cell lung cancer (NSCLC) and amplifications were associated with MET increased copy number. The description of tumors with two to three mutations in the PXN gene and the overrepresentation of GC to AT transitions were unexpected and needed confirmation. The aim of this study was to validate the incidence of PXN somatic alterations in NSCLC and to correlate them to other common genetic alterations. PXN mutations and copy number changes at PXN, EGFR, and MET loci were analyzed on DNAs from frozen tumor samples (n = 159) that had been previously screened for mutations at EGFR, KRAS, BRAF, ERBB2, STK11, PIK3CA, and TP53. We found PXN polymorphisms including nonsynonymous ones but no PXN amplification and only 1/159 (<1%) somatic tumor mutation F416L. In conclusion, we do not deny the possible involvement of PXN in cancer but our findings do not support a major role for PXN somatic changes in lung carcinogenesis.