The Epstein Barr virus (EBV) is causally associated to several tumors of epithelial and lymphoid origin. The cancerogenic role in other than B cells has not been proven. This virus has been considered as a target in the effective diagnosis of EBV-associated tumors. For this purpose, molecular biology methods to measure EBV DNA load in the circulation of patients suffering from EBV-related cancers have been recently developed. In this review, we discuss the role of EBV DNA determination, the technical limitations of molecular assays measuring viral load and their impact on the clinical management of patients with EBV-associated tumors arising in the immunocompetent host. Several studies have recently clarified the biological and clinical characteristics of herpesvirus-associated tumors. However, some additional issues must be clarified before introducing viral load determinations into clinical practice. Firstly, since the various EBV-related tumors have different etiopathological and clinical characteristics, the most appropriate biological samples and analytical cut off values must be clearly defined in each group of patients. Secondly, a standardization of the assay, including the definition of the gene segment to be amplified, the use of an international reference for the standard curve and disease-related cut-off values, is strongly required. Thirdly, the interpretation of laboratory data may benefit from an improved design of the studies and obtaining an aggregate of patients from different institutions, pooling these together, in order to have a sample size that is adequate to reinforce the statistical power of the studies.