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Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin’s lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.