Circulating cell-free DNA (cf-DNA) is characterized as extracellular DNA that may be present in the blood of healthy individuals in low concentrations. Cf-DNA is released by apoptosis or necrosis into the bloodstream. Increased levels are found in pathological conditions, such as inflammation, autoimmune diseases, or stress. Significant increase of cf-DNA is particularly evident in patients with malignancies, especially in the advanced stages of the disease. In this case, the tumor specific cf-DNA is released by necrosis from the cells of primary tumor and metastases. Recently, many studies concentrate on the so- called ‘liquid biopsies’ that allow detection of circulating tumor cells and circulating nucleic acids from peripheral blood for tumor diagnostics. Quantitative methods and detection of genetic and epigenetic alternations of cf-DNA in patients with different malignancies have potential applications in molecular diagnosis, prognosis, monitoring of disease progression and response to treatment. This review focuses on potential utility of cf-DNA as a blood biomarker in selected solid tumors and hematologic malignancies.