Immunoproliferative small intestinal disease is a distinctive lymphoproliferative disorder. Among these disorders, it is the only disease associated with a specific and characteristic abnormal protein, and also an identifiable, at least in some patients, early phase with a benign-looking histo-pathologic expression. Whether the disease at this stage is malignant or not is not known. Treatment of this early phase with antibiotics may cause remission in some patients. This observation is significant and raises the question of chemoprevention in lymphomas. In contrast to primary nonimmunoproliferative small intestinal lymphomas, in which the pathology in the intestine is usually focal and involving specific segments of the intestine and leaving the segments between the involved areas free of disease, the pathology in immunoproliferative small intestinal disease is diffuse, with a mucosal cellular infiltrate involving large segments of the intestine and sometimes the entire length of the intestine, thus producing malabsorption. Preliminary recent epidemiological data have shown a decrease in the incidence of this disease in endemic areas, and therefore environmental factors are suspected to play a major role in its pathogenesis. Additional research is indicated not only to understand this specific lymphoproliferative disorder but also to understand lymphomas in general.