In this study, we have investigated a potential association between Type 2 diabetes mellitus and its treatment with the risk of lymphoma. Here, we report on 565 incident lymphoma (non-Hodgkin and Hodgkin), multiple myeloma, and chronic lymphocytic leukemia cases and 601 hospital controls in a Spanish multicentric case-control study. Information on diabetes mellitus diagnosis and treatment was obtained through personal interview together with information on other known or putative risk factors for lymphoma. The average age of the study population was 59 years. A medical diagnosis of diabetes was reported by 11% of the controls and 16.3% of cases. Patients with diabetes mellitus not treated with drugs were at an increased risk for lymphoma (OR=1.73, 95%CI=1.11, 2.68), and particularly for multiple myeloma (OR=2.80, 95%CI=1.40, 5.59). Patients treated with insulin had a non-significantly reduced risk for lymphoma (OR=0.70, 95%CI=0.29, 1.67). If replicated, this effect could be explained by a disappearance of hyperinsulinaemia in patients requiring insulin or to the continuous stimulation of the immune system by insulin.