Both cell free DNA (cfDNA) and circulating tumor cells (CTC) represent important possible templates for mutation analysis of clinical samples. Each template has different theoretical advantages for a clinical test. cfDNA is very easy to access and isolate, while CTC can provide both DNA as well as RNA for clinical testing. In addition, the templates may reflect different aspects of cancer biology. Cynvenio has tested head-to-head cfDNA and CTC DNA using LiquidBiopsyTM coupled with Ion TorrentTM next-generation sequencing of normal and tumor samples. Both cfDNA and CTC samples provided sufficient quantity and purity of the limited number of tumor genomes for a direct sequencing clinical research test. No whole genome amplification was involved. The test for comparison purposes consisted of coupling these CTC and cfDNA purification technologies to an amplicon re-sequencing panel of 50 cancer-associated genes using a CLIA-validated sequencing pipeline for SNV mutations with a sensitivity of 1%. Typically, this pipeline can isolate, extract, sequence and analyze blood borne cancer cells in 7 days. In the CLIA setting, the validated DNA sequencing process, when applied to breast cancer tumor samples, has demonstrated useful data. The data suggest that cfDNA and DNA recovered from tumor-derived blood cells are complementary and may represent different aspects of cancer biology.