We report on an 83-year-old male with chronic neutrophilic leukemia (CNL) associated initially with IgM monoclonal gammopathy and later with B cell chronic lymphocytic leukemia (CLL), in which the clone differed from that of the preceding monoclonal gammopathy. At initial presentation, the patient had hepatosplenomegaly, leukocytosis (29100 x 10(6)/l) with an increase of mature neutrophils (83%), 20q- chromosomal abnormality, an increased leukocyte alkaline phosphatase score, elevated serum levels of vitamin B12 and uric acid, a low serum level of granulocyte colony-stimulating factor, and high serum IgM (1015 mg/dl: lambda type M protein). Thereafter, lymphocytosis developed gradually. Three years after the initial presentation, the patient had no serum M protein, but showed evidence of leukocytosis (36600 x 10(6)/l) with 20q- chromosomal abnormality and an increase of mature neutrophils (51%) and small lymphocytes (43.5%), CD5+/19+/20+/HLA-DR+ and surface membrane IgM+/D+/kappa+. Gene rearrangements of the immunoglobulin heavy and kappa light chains were also present. To our knowledge, this is the first reported case of CNL associated with CLL.