In the present study, we used DNA profiling to measure genomic instability in 22 patients with non-small cell lung cancer (NSCLC). Genomic instability was correlated with gender, the age of the patients at the time of diagnosis, the NSCLC subtype, histological grade and stage of the tumor, necrosis presence in the tumor and lymph node invasion. Genomic instability was significantly higher in patients older than 50 and those with adenocarcinoma compared to squamous-cell carcinoma. Most importantly, genomic instability significantly decreased as the tumor grade increased. Extensive genomic instability in the early carcinogenesis could be the prerequisite for NSCLC progression.