A 61-year-old woman presented with hepatosplenomegaly, systemic lymphadenopathy, anemia, and thrombocytopenia. Peripheral blood and bone marrow examination showed atypical lymphoid cells with villi. Immunophenotyping of these cells was CD19+CD20+CD5-CD10-CD23-, and light chain restriction (kappa) was positive. To confirm the diagnosis histologically, we performed a splenectomy and diagnosed the patient's disease as splenic marginal zone lymphoma (SMZL). She rapidly recovered normal hematological parameters and gallium-67 citrate scan showed no increased uptake. Two months after the splenectomy, however, she was readmitted with findings of 15% blasts in the peripheral blood and massive infiltration of the bone marrow by large blastoid cells. Laboratory evaluations were positive for monoclonal IgM-kappa protein. Under acute renal dysfunction, we performed a CT scan that showed bilateral enlargement of the kidneys with features suggestive of an infiltrative process besides systemic lymph node enlargement. A kidney biopsy established the diagnosis of lymphoma with renal infiltration. SMZL is characterized by an indolent clinical course, and no previous report has described SMZL with bilateral renal invasion. Complete remission was obtained after 3 cycles of chemothreapy (R-CHOP). She is undergoing 3 more courses and remains in remission 6 months after the rapid progress of her illness.