Summary Up to 10%–15% of diffuse large B‐cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the ‘Elderly Project’, on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV−) cases. A total of 89 HCV+ patients were identified out of 1095 evaluated for HCV serology (8.1%). The HCV+ patients were older, less fit, and had frequent extranodal involvement. The cell‐of‐origin determination by Nanostring showed that HCV+ cases less frequently had an activated B‐cell profile compared to HCV− patients (18% vs. 43%). In all, 86% of HCV+ patients received rituximab‐cyclophosphamide, doxorubicin, vincristine (Oncovin) and prednisone (R‐CHOP)‐like immunochemotherapy. Grade 3–4 liver toxicity occurred in 3% of cases. Among centrally reviewed cases confirmed as DLBCL, the 3‐year overall survival of HCV+ patients was very similar to HCV− (63% vs. 61%, p = 0.926). In all, 20 HCV+ patients were treated with direct‐acting antiviral agents (DAAs), with good tolerance and sustained virological response in all cases. The 3‐year progression‐free survival for this subgroup was excellent (77%), suggesting DAAs' possible role in reducing the risk of relapse by eliminating the viral trigger.