We investigated EBV viremia in matched serum and peripheral blood mononuclear cells (PBMCs) from one of the largest Italian cohort of Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) patients (N=34). By using a LMP-1 real-time PCR assay, we found that EBV DNA detection rate was 74% (median 8417 copies/ml) and 24% (median 164 copies/10(6)cells) on serum and PBMCs, respectively. Significantly higher serum EBV DNA levels were detected in patients with advanced UCNT (nodal stage N2 versus N0-1 and N3 versus N0-1, P=0.03 and 0.018; overall stage IV versus I-II, P=0.03). During the follow-up, there was also a statistically significant difference of EBV DNA viral load between patients with and without clinical relapse (P=0.008). We concluded that serum EBV DNA reflects the biological activity of the UCNT and may be a prognostic factor also in a low-incidence region.