Circulating DNA is an emerging biomarker in various types of cancer. It is generally believed that DNA released from apoptotic cells is uniformly truncated to small DNA fragments with 185-200 base pair (bp), whereas DNA produced by malignant cells varies in size (most of these are longer DNA fragments). Recently, the application of circulating DNA integrity indexes, represented by the ratio of the longer DNA fragments concentration to the shorter ones, has been reported in different cancers. This review will summarize the recently reported assays for detection of the circulating cell-free DNA (ccf-DNA) integrity and their clinical utility.