Patients with Gaucher disease have an increased risk of malignancies, especially the lymphoreticular type. To our knowledge, this is the first reported case of Gaucher disease diagnosed during the workup and diagnosis of a splenic marginal-zone lymphoma with progression to diffuse large B-cell lymphoma. There are several theories as to how Gaucher disease leads to malignancies. The accumulated glucocerebroside in the reticuloendothelial organs, histologically visible as Gaucher cells, is thought to provide chronic antigenic stimulus to the immune system. Polyclonal hypergammaglobulinemia develops, and monoclonal populations of lymphocytes and plasma cells may arise from this premalignant proliferative state. How Gaucher disease is related to nonlymphoid malignancies remains unclear.