The aim of this study is to detect the possible role of hepatitis C Virus (HCV) in lymphomagenesis. HCV-RNA and anti-HCV antibodies were studied in tissue and serum samples taken from patients with non-Hodgkin's Lymphoma (NHL). The prevalence of HCV, the clinical presentation of these cases, and association with histologic subtypes were determined. RT-PCR was used to detect the HCV-RNA in serum and tissue samples. The anti-HCV antibodies were tested with microparticle enzyme immunoassay. Immunohistochemistry with the ABC method was used to detect the HCV core protein in HCV-RNA(+) cases. RNA could be detected in 30 of 35 cases, and other tests were performed in these 30 samples. HCV-RNA was detected in 11 tissue samples (11/30, 37%). HCV core protein was studied in 10 of 11 HCV-RNA(+) cases, and 1-3% nuclear staining was found in only 2 samples. Serologically, HCV-RNA was detected in 7 of 30 samples (23.3%) and anti-HCV antibody was detected in 3 of 30 samples (10%). Detection of HCV-RNA in 37% of the lymphoma tissue samples suggests that HCV may have a role or is a contributing factor in the pathogenesis of lymphoma. The very low HCV core protein in lymphoma tissues may be due to the low viral load in lymphoid tissues and/or higher sensitivity of the PCR method. Detection of anti-HCV antibody in only three cases may be associated with undetectable levels of antibodies due to the immune deficiency in cases with NHL. (C) 2004 Wiley-Liss, Inc.