The morphologic, immunologic, genotypic, and functional properties of peripheral blood and bone marrow cells or cultured cells from two patients with a clinically aggressive non T, non B natural killer cell lymphoma/leukemia (ANKL/L) were described. The leukemic cells possessed medium to large granules in the cytoplasm, antigens against CD 38, CD 2, OKIal, and NKH-1 (N 901) monoclonal antibodies on their cell-surface, and also showed a high natural killer (NK) activity. In addition, these ANKL/L belonged to neither T-nor B-cell lineage, proved by studying clonal gene rearrangement for the T beta and T gamma receptor, and immunoglobulin. After we compared and investigated them with 9 cases of ANKL/L reported in other institutions, concerning immunophenotype, genotype and function, we reached the conclusion that the existence of ANKL/L originating from the third lineage in lymphoid cells is an obvious fact, suggesting this new clinical entity. It is important that all patients who have this type of a clinical disorder be diagnosed that there is no effective form of therapy at present.