Circulating tumor DNA (ctDNA) is now being extensively studied as it is a noninvasive "real-time"biomarker that can provide diagnostic and prognostic information before, during treatment and at progression.These include DNA mutations, epigenetic alterations and other forms of tumor-specific abnormalities such as microsatellite instability (MSI) and loss of heterozygosity (LOH).ctDNA is of great value in the process of cancer treatment.However, up to date, there is no strict standard considering the exact biomarker because the development and progression of cancer is extremely complicated.Also, results of the studies evaluating ctDNA are not consistent due to the different detection methods and processing.The major challenge is still assay sensitivity and specificity for analysis of ctDNA.This review mainly focuses on the tumor specific DNA mutations, epigenetic alterations as well as detecting methods of ctDNA.The advantages and disadvantages will also be discussed.