Three patients, one with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia (CML) and two with primary acquired myelodysplastic syndromes (MDS), have been identified to have a t(3;21)(q26;q22). In the patient with CML, the t(3;21) was detected only in the blast phase. The t(3;21) as the sole abnormality appeared at presentation of MDS [refractory anemia with excess blasts (RAEB)] in one patient and remained as such when progression to RAEB in transformation (RAEB-t) occurred. The other patient with MDS had the t(3;21), in addition to other changes, during the progression of the disease. Thus, t(3;21) may characterize myeloid crises of clonal hematopoietic stem cell disorders (HSCD) and indicates a poor prognosis. As a primary cytogenetic event it may be also involved in the genesis of myelodysplasia with subsequent leukemic transformation.