The first studies of monoclonal B-cell lymphocytosis (MBL) in the general population were conducted as part of environmental health investigations that began in 1991. MBL was observed as an unexpected finding when blood samples were immunophenotyped by two-colour flow cytometric methods in common use at that time. The initial observations led to a workshop in 1995, at which case definitions were considered and medical follow-up investigations were recommended. Medical follow-ups were conducted in 1997 and 2003. A total of eight cases of confirmed MBL and three cases of presumptive MBL were identified. This review summarizes the findings from those investigations and discusses the issues related to using MBL as a biomarker in environmental health research and population-based studies.