Cell-free tumor-specific and normal DNA are released into the blood circulation by cellular necrosis and apoptosis. We examined whether circulating DNA in blood of patients with colorectal cancer could be used as an additional marker for diagnosis and response to therapy. The concentration of circulating cell-free DNA in the blood of 55 patients with advanced colorectal cancer and 20 healthy donors was measured. One to four follow-up serum samples from 14 patients were also available. Patients with colorectal cancer had a wide range of DNA concentrations in their blood. The calculated values were between 22 and 3922 ng/mL DNA, with a mean and median value of 1157 ng/mL and 868 ng/mL, respectively. In contrast, the average concentration of cell-free DNA in the serum of healthy donors was significantly lower (5–16 ng/mL). During therapy the levels of serum DNA were not constant, but fluctuated, regardless of the chemotherapy used. High DNA levels of >1000 ng/mL of blood significantly correlated with a shorter survival (P= 0.02). Quantitative analysis demonstrates that elevated DNA levels can be detected in blood of patients with colorectal cancer and may be a useful tool in combination with other tumor markers for detection of colorectal cancer.