ABSTRACT Clinical trial results indicate that lenalidomide, an immunomodulatory drug, is a promising treatment in relapsed/refractory non-Hodgkin lymphoma (NHL). This retrospective multicenter study was conducted in relapsed/refractory NHL patients treated with lenalidomide monotherapy through a Named Patient Program in Italy. Principal endpoints were overall response rate (ORR), safety, and overall survival (OS). The ORR in 64 evaluable patients was 42.2% and was similar among patients receiving 10, 15, or 25 mg/day lenalidomide. Response rates in patients with mantle cell, diffuse large B-cell, and follicular lymphoma were 45.5%, 42.1% and 20%, respectively. Among patients who responded to most recent prior therapy, ORR was 50.0% versus 36.8% in refractory NHL patients. Mean duration of response in patients receiving any lenalidomide dose was 10.5 months; 1-year progression-free survival and OS were 50.3% and 82.6%, respectively. These findings suggest lenalidomide is effective and safe for heavily pretreated NHL patients in the clinical setting.