Epigenetic changes have been shown to play an important role in carcinogenetic processes. Out of these changes, the most studied one is tumor growth suppressor gene promoter hypermethylation that is one of the key mechanisms for increasing or decreasing gene expression in non-small cell lung cancer (NSCLC). The changes occurring in the tumor stroma and apparently normal tissues surrounding the tumor, the so-called cancerization fields, have a profound effect on tumor formation and progression. Epigenetic changes in the tumor and surrounding tissue were analyzed to identify these in different histological types of NSCLC, to estimate the extent of the study changes in the tumor-adjacent tissue and to reveal their possible associations with the clinical and morphological parameters of patients. Tumor and adjacent apparently normal tissue samples from 110 patients diagnosed as having NSCLC served as the material for investigation. The promoter hypermethylation of the RASSF1A (3p21.3), FHIT (3p14.2), DAPK1 (9q21.33), CDH1 (16q22.1), CD44 (11p13), TIMP3 (22q12.3), and MGMT (10q26.3) genes was analyzed using methylation-sensitive restriction polymerase chain reaction and bisulfite sequencing. Epigenetic changes were found in one of the study genes in 95% of the patients with NSCLC. In the latter, the rate of tumor epigenetic changes was 70% for the RASSF1A gene, 52% for the FHIT gene, and 17% for the DAPK1 gene. Statistically significant associations were found between the promoter hypermethylation of the CDH1 and CD44 genes and squamous cell cancer and between the concurrent promoter hypermethylation of the RASSF1A and FHIT genes and late disease stages (III-IV) with regional lymph node metastases. The epigenetic changes in the DAPK1 gene were shown to be associated with tumor spread. The epigenetic changes found in the promoters of the RASSF1A and FHIT genes may be regarded as markers for unfavorable prognosis in the disease and the promoter hypermethylation of the DAPK1 gene may be considered as a metastasis-associated marker.