This study was designed to investigate whether natural IgG antibodies against POU domain class 5 transcription factor 1 (POU5F1), tumor necrosis factor‐α (TNF‐α), and the combination of CD25, VEGFR1, and MUC1 could play an anti‐tumorigenic role against developing NSCLC. This evidence concerns the gene POU5F1 and non-small cell lung carcinoma.