In the present study, we investigated the prognostic value of RUNX3, H3K27me3, and EZH2 immunohistochemically in 188 surgically resected NSCLC patients, demonstrating that NSCLC patients with a cellular signature of simultaneous expressions RUNX3 and H3K27me3 would have better outcome and longer OS, irrespective of their histology and TNM staging. This evidence concerns the gene EZH2 and non-small cell lung carcinoma.