In a prospective study on 44 cases of T-cell origin acute lymphoblastic leukemia, 20 patients were found to display an immature immunophenotype (CD7+, CD4-, CD8-, CD1-) and were classified as T-stem cell leukemia (T-SCL). Twenty-four patients expressed CD4 and/or CD8 antigens on their blast cells, designated T acute lymphoblastic leukemia (T-ALL). The T-SCL subset showed a significantly higher median age, a more frequent incidence of extramedullary leukemia, a morphology L1 in most cases, and a poor response to treatment in terms of either complete remission rate or median survival duration. In addition, significant differences between the two groups were found in evaluating the number of days of blast disappearance from peripheral blood, of CR achievement, and of neutrophils and platelets recovery. We conclude that T-SCL represents a distinct clinical entity, characterized by a poor response to ALL conventional chemotherapy. Alternative therapeutic approaches should be developed for patients suffering from this form of leukemia, to modify its severe prognosis.