Circulating free DNA (cfDNA) are degraded DNA fragments released to the blood plasma. cfDNA can be used to describe various forms of DNA freely circulating the bloodstream, including circulating tumor DNA (ctDNA) and cell-free fetal DNA (cffDNA). Elevated levels of cfDNA are observed in cancer, especially in advanced disease.There is evidence that cfDNA becomes increasingly frequent in circulation with the onset of age. cfDNA has been shown to be a useful biomarker for a multitude of ailments other than cancer and fetal medicine. This includes but is not limited to trauma, sepsis, aseptic inflammation, myocardial infarction, stroke, transplantation, diabetes, and sickle cell disease. cfDNA is mostly a double-stranded extracellular molecule of DNA, consisting of small fragments (70 to 200 bp)  and larger fragments (21 kb). and has been recognized as an accurate marker for the diagnosis of prostate cancer and breast cancer.

Some publications confirm the origin of cfDNA from carcinomas and cfDNA occurs in patients with advanced cancer. Cell‐free DNA (cfDNA) is present in the circulating plasma, also in other body fluids.

The release of cfDNA into the bloodstream appears by different reasons, including the primary tumor, tumor cells that circulate in peripheral blood, metastatic deposits present at distant sites, and normal cell types, like hematopoietic and stromal cells. Tumor cells and cfDNA circulate in the bloodstream of patients with cancer. Its rapidly increased accumulation in blood during tumor development is caused by an excessive DNA release by apoptotic cells and necrotic cells. Active secretion within exosomes has been discussed, but it is still we don't know whether this is a relevant or rather minor source of cfDNA.

cfDNA circulates predominantly as nucleosomes, which are nuclear complexes of histones and DNA. They are frequently nonspecifically elevated in cancer but may be more specific for monitoring cytotoxic cancer therapy, mainly for the early estimation of therapy efficacy.