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Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is associated with increased risk for certain cancers, but relatively little is known about the risk for these patients to develop additional B cell malignancies. Here, we review the available epidemiological data on multiple B cell malignancies in CLL, discuss diagnostic methods and proper pathologic evaluation to distinguish CLL from other B cell malignancies, and address clinical challenges and unmet needs in caring for CLL patients with unrelated B cell malignancies and disease transformation. Considerations include CLL patients with unrelated monoclonal B cell lymphocytosis, biclonal CLL, secondary B cell non-Hodgkin lymphomas, and Richter syndrome – both clonally related transformation and de novo large B cell lymphoma. We address the challenges that remain in order to better understand the underlying risk factors and biology that …