Since the discovery of cell-free DNA (cfDNA) in human blood, most studies have focused on diagnostic and prog-
nostic uses of these markers for solid tumors. Except for some prenatal tests and BEAMing, cfDNA analysis has not
yet been translated to clinical practice and routine application appears distant. This can be attributed to overlap-
ping factors: (i) a lack of knowledge regarding the origin and function of cfDNA, (ii) insufficient molecular char-
acterization, and (iii) the absence of an analytical consensus. In this review, we address the latter determinant
and focus specifically on quantitative analysis of cfDNA. While the literature reports limited value for a single
quantitative assessment, cfDNA kinetic assessment will be an essential component to qualitative characteriza-
tion. In order to establish quantitative analysis for accurate kinetic assessments, process optimization and stan-
dardization are crucial. This report elucidates the most confounding variables of each preanalytic step that
must be considered for optimal analysis.