The choice to select cfDNA alone to differentiate malignant and benign lung nodules detected by LDCT appears reasonable in light of the cfDNA physiopathology assumed in cancer subjects that comprises several mechanisms of fragmented DNA release from alive or dead tumor cells, including apoptosis, necrosis, production of neutrophil extracellular traps and extracellular vesicles, and pyroptosis (caspase 1-dependent cell death) [1,2,3], but also from leukocytes [4,5]. This evidence concerns the gene CASP1 and neoplasm.