Cytogenetic investigations have distinguished at least 3 distinct clinical-cytogenetic syndromes of hematopoietic malignancy with structural rearrangement of 3q. The majority of cases have breakpoints at both 3q21 and 3q26, frequently associated with monosomy 7, abnormal thrombopoiesis, and adverse outcome. Cases with only one of these breakpoints may have milder features of the syndrome. A subgroup with t(3q;5q) occurs in younger patients, occasionally with megakaryocytic dysplasia but rarely having thrombocytosis. The t(3;21) is encountered in secondary leukemias or after chemotherapy of myeloproliferative disorders. The genetic deregulations associated with each of these syndromes involve distinct genes on 3q. The majority of cases of acute leukemias with 3q rearrangements have a poor prognosis and do not respond to current modes of therapy.