The incidence of non-Hodgkin lymphomas increases with age. Non-pegylated liposomal formulations of doxorubicin (Myocet®) reduce systemic and cardiac toxicity especially in the elderly, who often have cardiac diseases. We treated 80 patients (mean age 70.9 years) with poor-risk diffuse large B-cell lymphoma with the R-COMP 21 regimen (Myocet® 50 mg/m(2), cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2), rituximab 375 mg/m(2), prednisone 100 mg/day). In all, 82.5% and 13.7% patients showed complete and partial responses, respectively. Sixty-two of the 80 patients are alive and disease-free (77.5%), while 3/80 are alive with active disease and 15 patients (18.7%) have died (median follow-up: 31 months). The estimated probability of overall survival at 12/24 months from admission was 93.5/87.3%, respectively. There were no therapy-related cardiac events and the ejection fraction improved (from 51.6 ± 6.9% to 54.2 ± 3.9%). Grade 3-4 neutropenia occurred in 22% of patients. We concluded that Myocet® shows both efficacy and tolerability, mainly at the cardiac level.