We report 2 cases of splenic postchemotherapy histiocyte-rich pseudotumor. Each patient had a history of diffuse large B-cell lymphoma, treated with multiagent chemotherapy. Computed tomography scans performed on both patients showed splenic masses. A positron emission tomography scan performed on 1 patient showed increased metabolic activity. The preoperative diagnosis in both patients was recurrent lymphoma, prompting splenectomy. The splenectomy specimens showed multiple, tan-white, firm nodules, up to 3.5 cm in diameter, that were histologically composed of central necrotic B cells (CD20+/CD3-), consistent with necrotic lymphoma, surrounded by numerous lipid-laden (xanthomatous) histiocytes. Clinical staging studies at the time of splenectomy showed no other sites of disease. We conclude that these histologic and immunophenotypic findings represent chemotherapy-induced tumor necrosis with a florid histiocytic reaction mimicking residual viable lymphoma. Others have used descriptive terminology or the term xanthomatous pseudotumor for these lesions that have been only rarely reported in the spleen previously.