Monoclonal B lymphocytosis (MBL) is an asymptomatic clinical syndrome wherein small B cell clones are detectable in the peripheral blood. MBL is common in the adult population, with an estimated prevalence of greater than 3% among individuals over age 50. Most MBLs have an immunophenotype similar to chronic lymphocytic leukemia (CLL). Recently, MBL has been shown to be a precursor state for CLL, though most MBLs presumably do not progress to CLL. Therefore, there has been considerable interest in the biology of MBL to better understand the mechanisms of CLL leukemogenesis. We have investigated immunoglobulin heavy chain gene usage and clonality in MBL. These investigations reveal that most MBLs use mutated heavy chains typically associated with good-risk CLL, and that MBLs are frequently oligoclonal, rather than monoclonal. Deletion of chromosome 13q14 is also commonly observed. These and other ongoing studies may help illuminate the pathogenesis of CLL.