Epstein-Barr viral (EPV) DNA load as a non-invasive diagnostic and/or prognostic modality for Egyptian nasopharyngeal carcinoma (NPC) patients. Patients & Methods: All patients underwent fiberoptic direct nasopharyngoscopy for nasopharyngeal inspection and to obtained tissue biopsy of a suspicious growth for pathological examination and grading according to WHO pathological grading. Primary tumor extent was evaluated by both MRI and CT scanning. Two venous blood samples were collected; one prior to initiation of therapy and at 4-weeks after the last session of radiotherapy for quantitative PCR determination of EBV plasma DNA loads. For primary treatment: external radiotherapy and brachytherapy boost for patients with lesions staged T1/T2 N0 M0; external radiotherapy + concomitant chemotherapy +adjuvant chemotherapy and uni- or bilateral neck block dissection for persistent nodal disease at 3 months for patients with nodal lesions. Follow-up included nasopharyngoscopy three-monthly for 2 years. Results: The study included 45 patients; 23 patients (51.1%) had nodal involvement. According to TNM staging; 3 patients had carcinoma in situ, 6 had stage-I, 12 had stage-II, 15 had stage-III and 9 patients had stage-IV lesions; 22 lesions were WHO grade I, 14 were grade II and 9 lesions were WHO grade III. There was a positive significant correlation between WHO pathological and TNM staging. MRI detected local invasion in 12 patients (26.7%). Qualitative PCR detected EBV viral DNA in all blood samples. Using Quantitative PCR technique, mean EBV DNA plasma load was 2188±642 copies/ml. There was a positive significant correlation between mean plasma viral load and TNM stage and WHO grade. Post-treatment quantitative PCR detected EBV DNA only in 10 (22.2%) patients with a mean plasma level of 61.5±33.7 copies/ml that was significantly lower than pre-treatment levels. Conclusion: PCR quantitative estimation of plasma Epstein-Barr viral DNA load is a valuable diagnostic test that showed a positive significant correlation with both TNM staging and WHO pathological grading of patients with NPC and could be used to assess the response to applied therapeutic modalities. Considering Egypt as a non-endemic area for NPC, quantitative estimation of EBV plasma load could be used as screening test for patients presenting by symptoms suspicious of NPC. [Ahmed Houssein, Mosad M. Odah, Eman A. Badr, Mohamed Al-Sherbiny and Tamer El-Shiehk. Serum Epstein Barr Virus as a Biomarker in Nasopharyngeal Carcinoma. J Am Sci 2012;8(5):658-666]. (ISSN: 1545-1003). http://www.americanscience.org. 71 Keywords: Epstein Barr virus, Polymerase chain reaction, Diagnosis, Prognosis, Nasopharyngeal carcinoma