We describe the first three patients with a large granular lymphocytosis/lymphocytic leukemia and another blood malignancy. In two, a myeloproliferative disorder developed soon after the diagnosis of abnormal proliferation of large granular lymphocytes-natural killer (LGL-NK) cells, a myelodysplastic syndrome evolving to acute leukemia and a Philadelphia-positive chronic myelogenous leukemia. In these cases, LGLs expressed the phenotype of CD3+ NK and CD3- NK cells, respectively, and were clonal in the first patient as demonstrated by T-cell receptor gene rearrangement study. In the third case, a similarly clonal excess of LGLs, phenotypically CD3+ NK cells, was detected following a diagnosis of B-cell hairy-cell leukemia. Clinically, the concurrence of LGL proliferation and other leukemia did not seem to confer a worse prognosis on the patients. Although an association by chance remains a possible explanation, a common origin from an altered precursor cell for both myeloid and LGL proliferations in the first two cases is discussed, whereas in the third it might be related to the severe immune derangement frequently observed in hairy-cell leukemia.