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Abstract: Background: Nasopharyngeal carcinoma (NPC) is an Epstein–Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia. Objectives: To evaluate the clinical values of pre-treatment plasma EBV DNA levels in Malaysian NPC patients. Study design: Plasma EBV DNA levels were measured by quantitative PCR (Q-PCR) in a large and multi-ethnic cohort of Malaysian patients with NPC (n =459) and 72 control subjects. Results: We show for the first time that, compared to controls, NPC patients with stage I disease had significantly higher levels of EBV DNA (p <0.001). Further, the median level of plasma EBV DNA in stage IV patients with distant metastasis was >9-fold higher than those without systemic spread (p =0.001), suggesting plasma EBV DNA measurement could aid in the diagnosis of metastatic disease in advanced cases. Further, using a cut-off value of 8000copies/mL, we demonstrate that EBV DNA level is a strong predictor for overall survival of NPC patients. Conclusions: Our data show that pre-treatment plasma EBV DNA is a potential biomarker for early stage and metastatic NPC. We conclude that the quantification of plasma EBV DNA is a useful tool in developing countries to stratify patients for MRI or PET/CT scans where such imaging protocol is not routinely applied. [Copyright &y& Elsevier]