As a proof-of-concept study, we used a series of different BRAF p.V600E Reference Standard Variant Allele Frequency (VAF) and liquid biopsy samples obtained from a cohort of eight patients diagnosed with CRC and lung adenocarcinoma (LUAD) to test the three nucleic acid detection tools in order to define the most suitable method for DNA biomarker detection. The gene discussed is BRAF; the disease is colorectal carcinoma.