Molecular barcode technology eliminates PCR/sequencing errors and generally achieves an error rate of approximately 10−5, regardless of platform and assay conditions [3–5]. Thus, this technology is likely to be indispensable for NGS of cfDNA. However, it is not effective for removing artifacts introduced before PCR, such as those introduced by damage to genomic DNA during or before sample preparation. In addition, preexisting somatic mutations in normal cells  make it difficult to discriminate ctDNA from cfDNA originating from normal cells. Current knowledge regarding the prevalence of mutations in nuclear DNA is based on living cells, and comparatively little is known about mutations in DNA entering the circulation from dead/dying cells. Somatic mutations in normal cells might become more frequent just before death, especially under stress conditions, such as cancer.