Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China. Epstein-Barr virus (EBV) infection is an important etiological factor of NPC. The fact that EBV genome is present in almost all NPC tissues renders it an ideal tumor marker for NPC. To date, quantitative analysis of plasma EBV DNA has been shown to be clinically useful for the detection, monitoring, and prognostication of NPC. In addition, the molecular nature of circulating EBV DNA has recently been identified as that of free DNA fragments; it is not contained inside intact virions. By quantitative size analysis, it is further demonstrated that more than 80% of these DNA fragments are less than 180 bp in size. In this chapter, the clinical applications of plasma EBV DNA analysis and the protocols for the quantitative analysis of the size of circulating EBV DNA will be discussed.