The implementation of early-detection technologies and prognostic biomarkers are imperative, specifically in cities highly exposed to environmental carcinogens, such as PAHs and Arsenic. This study proposed to evaluate cfDNA levels and determine CNAs in serum cfDNA in LC and PNL patients. The study enrolled a total of 107 people, from the Metropolitan (N=51) and Antofagasta (N=56) regions, with medium or high LC risk. The cfDNA was isolated from serum aliquots using Qiagen QIAamp DNA mini kit. HMMs analysis in cfDNA, was used as a probabilistic model to determine an unknown sequence and defined Minimal Common Regions (MCRs) of recurring DNA gains and losses. This study shows that cfDNA levels increased during malignancy of LC but not significantly during premalignant lesions or pre-invasive stages. The cfDNA could be used as a complementary tool to prognosis and evolution of LC, with high precision (specificity of 87.3% and PNV of 76.4%). Additionally, the cfDNA carry some chromosomal aberrations related with the lung tumorigenesis process that could be used to confirm a suspected case of LC. Within these alterations our results suggest the loss of specific chromosomic fragments, contain genes related with inflammation response (SERPING1), humoral immune response (IGCK), innate immunity and epithelial integrity (CTNN1), tumor suppressor (MAP2K4, DMTF1 and ABCB4), and response to oxidative stress (COX10). In conclusion, these biomarkers in cfDNA, could have a great potential as screening methods in population with high risk for LC.