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Background: Splenic marginal zone cell lymphoma (SMZL) is a low grade B-cell lymphoma in which patients can have circulating villous lymphocytes and can show a peculiar intrasinusoidal bone marrow (BM) infiltration. Splenectomy is the reported treatment of choice for these patients. The objective of this study was to evaluate the effects of splenectomy on patients with BM lymphomatous infiltration., Methods: BM biopsies of 16 patients with SMZL were studied morphologically and immunohistochemically. In 12 patients, BM biopsies were taken before and after splenectomy. Four patients did not undergo splenectomy, and their BM biopsies were performed with an approximately 1 year interval., Results: BM infiltration ranged from 10% to 40% of overall cellularity and was mostly of the intrasinusoidal type. After splenectomy, BM infiltration tended to become frankly nodular and showed an increase in tumor burden. Nonsplenectomized patients showed an unmodified picture., Conclusions: Splenectomy seems to induce important changes in patients with BM infiltration, probably through the lack of microenvironmental factors on circulating cells. These effects suggest reconsidering the role of splenectomy in the treatment of patients with SMZL.