Background and study aim: Many recent studies showed that chronic infection with hepatitis C virus (HCV) is associated with increased risk for B-cell non-Hodgkin's lymphoma (NHL). The aim of this study is to evaluate the frequency of HCV infection in a series of de novo B cell non Hodgkin's lymphoma (NHL) patients and to correlate virological findings with clinicohistological features. Patients and methods: 50 patients with B cell NHL diagnosed by histopathology and immunophenotyping were recruited from Tropical medicine department and Oncology unit affiliated to Internal medicine department, Zagazig University hospitals. Gender and age matched controls (N = 50) were volunteers selected from relatives of patients. Study participants were subjected to history taking, clinical examination, routine and specific laboratory tests. Anti-HCV antibody was determined by ELISA for all study participants. HCV RNA PCR was done for all cases and HCV antibody positive controls. Appropriate radiologic examinations were performed. Results: Frequency of HCV infections were statistically significantly higher in B cell NHL patients than in controls (p = 0.004). ALT levels were statistically significantly higher in HCV positive patients than in HCV positive controls (p < 0.001) and HCV negative patients but without statistically significant difference (p = 0.067). There was no statistically significant difference in histologic types, grades and stages of NHL between HCV positive patients and HCV negative patients. Cryoglobulinemia showed no significant difference between studied groups. Conclusion: HCV has a strong association with de novo B cell NHL, not complicating essential mixed cryoglobulinemia (EMC).