In the past several decades, malignant lymphomas have been transformed from almost uniformly fatal illnesses to diseases that can be treated, with an expectation of long-term remission in a majority of patients. However, with the recognition of treatment efficacy also has come an appreciation of long-term sequelae. Among these late effects, the induction of a second cancer represents one of the most feared complications. For many years, acute nonlymphocytic leukemia has been the most frequently reported secondary malignancy; however, with increasing length of follow-up, solid tumors have replaced leukemia as the most commonly observed second cancers. The risk of second neoplasms depends on some treatment associations and on certain host-related factors. Less toxic treatment strategies need to be designed and appropriately tested in comparative trials. However, it is necessary to stress that, without effective therapy, the natural outcome of malignant lymphomas is death from progressive disease.