The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by north-American and south-European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). However, controversial data were reported from other areas. The review of available reports to data on HCV-associated LPD points to some features: predominance of low-grade malignant lymphoma, frequent involvement of extranodal sites, absence of particular HCV genotype distribution (except in Italy for genotype 2), important geographical seroprevalence discrepancies. In our experience in 43 cases of HCV-associated LPD in France, we noted a predominance of B-cell NHL (31/43 cases), and the frequency of LPD among HCV-infected patients approximates 2.5%. Pathophysiology hypotheses are discussed, particularly in view of the lympho tropism of HCV. HCV is frequently associated with type II mixed cryoglobulinemia, a benign monoclonal lymphoproliferation which sometimes evolves to overt B-cell lymphoma. The recent finding of HCV binding on CD81, a surface-expressed protein present on lymphocyte membrane, enhances the putative role of HCV in lymphomagenesis. Further investigations are needed to characterize interaction between B lymphocytes and HCV, and to determine putative cofactors involved in the multistep process leading to clonal lymphoproliferation in HCV patients.