Three cases of unusual lymphoid infiltrate forming nodular macroscopic masses in the liver were studied in the authors' surgical pathology laboratory. These lesions posed difficulty in diagnosis, and their differentiation from low-grade lymphoma was not possible on histopathologic evaluation alone. The liver masses were analyzed histologically and immunohistochemically as well as for clonal immunoglobulin heavy chain (IgH) and T-cell receptor gamma (TCR-gamma) gene rearrangements. The lesions were seen as solitary grossly distinct firm nodules in all three patients, measuring 0.4, 0.7, and 1.5 cm, respectively, in their greatest dimensions. Two were found in livers removed because of end-stage primary biliary cirrhosis at the time of orthotopic liver transplantation, and the third was an incidental finding during laparotomy. Microscopically, these were nodules composed of small lymphocytes, plasma cells, and immunoblasts, with varying degrees of admixed acute inflammatory cells and scattered lymphoid follicles. By immunohistochemistry and molecular studies, these were found to be reactive lymphoid proliferations. All patients are alive and well at 2, 4, and 13 years, respectively. It is concluded that these cases represent a unique type of nodular lymphoid lesion, which is probably an immune-mediated benign reactive hyperplasia. It constitutes an entity by itself and must be distinguished from low-grade lymphoma. For a definitive diagnosis, immunohistochemistry and molecular studies are required.