This study evaluated Epstein-Barr virus (EBV) DNA in sera of 42 patients with nasopharyngeal carcinoma (NPC) and 82 healthy individuals who had been infected previously with EBV. Thirteen of 42 NPC samples were positive for EBV DNA in their sera, whereas all 82 normal controls were negative. In addition, EBV typing between primary tumors and sera showed identical results, suggesting that serum EBV DNA represented tumor DNA. To evaluate the importance of the serum NPC DNA, clinical data and tumor phenotypes including age, sex, WHO type, EBV type, stage, tumor invasion, metastasis, and apoptosis were correlated with serum EBV DNA, and only apoptosis was found statistically significant. In conclusion, EBV DNA was detectable in the serum of some patients with NPC, represented tumor DNA, and might have clinical implications in the future.