The authors report the results of a hospital-based case-control study of all patients diagnosed with chronic myelomonocytic leukemia (CMML) (n = 36) from 28 participating hospitals over a 4-year period. Diagnoses were made by a single laboratory using 2001 World Health Organization (WHO) criteria. Subjects were matched to 2 control patients and interviewed concerning previous diseases, work histories, and exposures to potential etiologic agents. Peripheral blood and bone marrow findings revealed clinical features of both myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs), consistent with hematopoietic disease category of MDS/MPN. The frequency of clonal cytogenetic abnormalities in all CMML cases was 31%, with no consistent pattern identified. A select number of risk factors associated with occupational exposure, nonoccupational exposure, and prior medical or family history of disease were extracted from the questionnaire. The results were compared between the case and control subjects. A total of 5 study subjects (2 CMML cases and 3 control subjects) were determined to have had some benzene exposure. In addition, none of the highlighted risk factors associated with nonoccupational exposure to etiologic agents was significantly different among the study subjects. These results do not support an increased risk for developing CMML associated with historical exposures to benzene.