1 Dipartimento di Oncologia ed Ematologia, Università di Modena e Reggio Emilia, Modena 2 Medicina Interna, Oncologia e Gastroenterologia, Università di Pavia, Pavia 3 Dipartimento di Ematologia, Ospedale Spirito Santo, Pescara 4 Divisione di Ematologia, Azienda Ospedaliera Papardo, Messina 5 Ematologia e Trapianto Cellule Staminali, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (PZ), Italy Correspondence: Stefano Sacchi, Centro Oncologico Modenese, Policlinico, Largo del Pozzo 71, 4100 Modena Italy. E-mail: ssacchi{at}unimo.it Background: Improved treatment has increased the life expectancy of patients with non-Hodgkin’s lymphoma, but few studies have addressed the issue of second cancer in patients treated for diffuse large B-cell lymphoma. The aims of this study were to determine the incidence and time free of second cancers in this subset of patients. Design and Methods: We evaluated a cohort of 1280 patients with diffuse large B-cell lymphoma who were first treated between 1988 and 2003. We utilized the central database of the Gruppo Italiano Studio Linfomi , which includes data on demographics, clinical characteristics, laboratory parameters, treatment and follow-up of all patients with non-Hodgkin’s lymphoma enrolled in clinical trials. Results: After a median follow-up of 51 months, 48 patients had developed a second cancer: 13 hematologic malignancies and 35 solid tumors. The overall standardized incidence ratio in our cohort (with a median age of 58 years) matched that of the general Italian population. The incidence ratio of second tumors was age related, and the age groups 20–39 and 40–59 years showed an increased risk. Overall, the cumulative incidence of second cancer was 8.2% at 15 years. A multivariate analysis showed that older age at the time of diagnosis of lymphoma had a negative influence on the time free of second tumors. Conclusions: In our cohort, only young patients showed an increased incidence ratio of second malignancies, while the incidence ratio in patients aged over 59 years matched the incidence in the Italian general population. Demographics, baseline characteristics, laboratory parameters and treatment modalities did not have any significant impact on the incidence ratio of a second cancer. Key words: second malignancies, non-Hodgkin’s lymphoma, diffuse large B-cell lymphoma, DLBCL, risk factors, treatment.