SummaryVery low levels of circulating monoclonal B‐cell subpopulations can now be detected in apparently healthy individuals using flow cytometry. We propose the term ‘monoclonal B‐cell lymphocytosis’ (MBL) to describe this finding. The aim of this document is to provide a working definition of MBL for future clinical, epidemiological and laboratory studies. We propose that the detection of a monoclonal B‐cell population by light chain restriction is sufficient to define this condition in individuals not meeting the diagnostic criteria for other B‐lymphoproliferative disorders. The majority of individuals with MBL will have cells that are indistinguishable from chronic lymphocytic leukaemia (CLL). However, this blood cell clonal expansion of CD5+ or CD5− B‐lymphocytes is age‐dependent and immunophenotypic heterogeneity is common. Longitudinal studies are required to determine whether MBL is a precursor state to CLL or other B‐lymphoproliferative disease in a situation analogous to a monoclonal gammopathy of undetermined significance and myeloma. Future studies of MBL should be directed towards determining its relationship to clinical disease, particularly in individuals from families with a genetic predisposition to developing CLL.

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Summary Monoclonal B cell lymphocytosis (MBL) was detected in four unaffected first‐degree relatives (FDR) in a familial chronic lymphocytic leukaemia (CLL) kindred. The proband remains untreated and two male siblings have died. The four unaffected siblings have been followed for a five‐year period. All four FDR developed a kappa+CD5+ MBL detected by flow cytometry. Poymerase chain reaction (PCR) for IGHV rearrangement showed evidence of oligoclonality in three of these individuals. Single cell PCR of flow cytometric sorted kappa+ cells combined with Ig kappa light chain gene sequencing revealed further evidence of monoclonality in two of these individuals. Three of these individuals all showed evidence of hyper‐somatic mutations. The B‐cell repertoire in unaffected FDR in familial CLL offers a new area to investigate the interface between the immune system and lymphoid neoplasm.