In the present study we report the results of the EBV-specific antibody response in 30 Italian NPC patients, 20 other head and neck tumor patients and 20 healthy controls. Histopathologically, the tumors were classified as squamous cell carcinoma (WHO 1), nonkeratinizing carcinoma (WHO 2) and undifferentiated carcinoma (WHO 3). Immunofluorescence tests were performed in order to evaluate the antibodies against VCA, EA and the EBV nuclear antigen (EBNA), and the antibody dependent cellular cytotoxicity test was used to detect the EBV specific antibodies against membrane antigens. IgG and IgA antibodies to EBV VCA and IgG antibodies to EA were significantly and consistently higher in the NPC patients than in other patients or controls. Moreover, only the WHO 2 and WHO 3 histological types of NPC resulted associated with EBV. ADCC titers ranging from 1:480 to 1:15360 have been determined; low ADCC titers were prevalent among the VCA-IgA positive donors, while VCA-IgA negative donors presented high ADCC titers. Our results look consistent with other previous results in low-risk and high-risk areas. In conclusion, EBV serology seems to be extremely useful for diagnostic purposes; however, in order to assess a prognostic value of the above markers, a greater number of patients followed for a longer period is needed.