The recent interest in cell-free tumor-derived DNA in the plasma and serum of cancer patients has opened up numerous diagnostic possibilities. One type of tumor-derived DNA that has been detected in plasma/serum is viral DNA. One example of circulating viral nucleic acid is Epstein-Barr virus (EBV) DNA, which has been found in the plasma and serum of patients with nasopharyngeal carcinoma (NPC), certain lymphomas, and gastric carcinoma. Quantitative analysis of circulating EBV DNA in NPC has demonstrated a positive correlation with disease stage and a strong relationship with clinical events, as well as being of prognostic importance. For EBV-associated lymphomas, quantitative EBV DNA analysis has also been found to correlate closely with clinical progress. It is expected that plasma/serum EBV DNA analysis will soon be incorporated into the routine investigative protocol of EBV-associated malignancies.