Cytogenetic translocations involving chromosome band 19p13, the site of the E2A gene, have previously been reported in pediatric acute lymphoblastic leukemias (ALL) in association with a precursor-B cell immunophenotype and poor prognosis. We studied the frequency, pathologic findings, and clinical course of adults with leukemia with 19p13 translocations. Six patients with t(1;19) (q23;p13) and one patient with t(17;19)(q21;p13), all with ALL, were identified over an 8-year period from among 183 adult ALL patients (2.7%); t(1;19) was observed in 2.2% and t(17;19) in 0.5% of these patients. The seven patients (four females and three males) ranged from 18 to 59 years of age (median 33). All cases had a precursor-B cell immunophenotype, and a distinctive expression of surface markers (CD10, CD19, TdT, and HLA-Dr positive, usually negative for CD20, CD34, and negative for myeloid-associated antigens CD13, CD14, and CD33). The blast cells in one case expressed CD15. All patients were treated with combination chemotherapy and three patients received allogeneic bone marrow transplantation. All patients had early (range 6-20 months) relapses, and died due to progressive disease 7-29 months after diagnosis. Similar to pediatric patients, adults with 19p13 leukemias usually do not respond to intensive therapy and have short survival. The poor prognosis of this group of adult ALL patients highlights the importance of detecting 19p13 translocations by cytogenetic analysis or molecular studies.