This report describes a single institution's recent experience with six patients fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common cytogenetic abnormalities characteristic of myeloid disorders were detected. Two patients demonstrated clonal evolution during the course of the disease. All responded initially to therapy with hydroxyurea with control of leukocytosis and reduction in splenomegaly. Three patients eventually became refractory to hydroxyurea, manifesting progressive neutrophilia without blastic transformation. Aggressive chemotherapy to control progressive leukocytosis resulted in death due to cytopenias in two of these patients. The third patient received less intensive chemotherapy and died of progressive disease. One patient died after transformation of the disease into undifferentiated acute myeloid leukemia. Two patients remain alive with stable disease on hydroxyurea therapy, 12 and 54 months after initial diagnosis. Chronic neutrophilic leukemia is a rare clinicopathologic entity that can be distinguished from chronic myelogenous leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and myelodysplastic syndrome. The clinical course is heterogeneous, with a definite risk of death from either blastic transformation or progressive neutrophilic leukocytosis. Continued study and reporting of these cases must be encouraged.