Recent progress in circulating tumor DNA (ctDNA) analyses now allows the monitoring of tumor genomes by noninvasive means. Multiple studies have shown that it is possible to reconstruct tumor genomes from plasma DNA. There are many biological and technical aspects as well as challenges for a widespread implication of ctDNA in cancer diagnostics. The length of ctDNA is quite short around 168 bp, and recent studies with high-throughput sequencing presented that that more than 80% of ctDNA fragments in cancer patients’ plasma were below 145 bp, reflecting the high degree of fragmentation through apoptotic mechanisms. Furthermore, ctDNA is rapidly cleared in plasma, liver, spleen and kidney with half-life being estimated to 16 minutes. Therefore, immediate sample processing or use of specific tubes with preservative solution is strongly recommended.　　Owing to the high degree of fragmentation and its low concentration in the circulation, detecting tumor-derived ctDNA requires sensitive assays. However, those genes without hot-focus mutations may need whole gene sequencing and specialized next-generation sequencing technology may be needed for accurate detection of low-level mutations with high specificity, including those using unique molecular indexes. Detecting ctDNA could be utilized in diagnosis of early tumors, detecting mutations as potential therapeutic target, establishing prognosis, and monitoring tumor burden during treatment. Although the analysis of ctDNA is a promising area, harmonization of preanalytical and analytical procedures is needed to provide clinical standards to validate the liquid biopsy as a clinical biomarker in well-designed and sufficiently powered multicenter studies.