Although the recognition of hybrid acute leukemia (HAL) is still controversial, several reports have described cytogenetic findings in these leukemias over the last 3 years. A distinct chromosomal profile appears to be associated with different immunologic subsets of HAL. The classical t(15;17), and inv(16) as well as abnormalities of the long arm of chromosome 5 and/or 7 are preferentially associated with acute myeloid leukemia (AML) with T-cell features; the t(8;21)(q22;q22), the Ph chromosome, and 11q23 rearrangements are more frequently found in AML with B-cell features; the Ph chromosome, t11q23 and 14q32 breaks without rearrangements of the immunoglobulin heavy chain gene may be associated with acute lymphoblastic leukemia (ALL) with myeloid markers. In addition, some chromosome aberrations may be encountered more frequently in acute leukemia with major phenotype deviations than in unselected cases of acute leukemia: namely the Ph chromosome, 11q23 rearrangements, and +13. These chromosome changes appear to be associated with a low complete remission (CR) rate. An association has been documented in some patients with ALL between the presence of the t(9;22) and a minor myeloid component consisting of 5-15% blast cells with myelomonocytic features, raising the possibility that a diagnosis of bilineal acute leukemia would be more appropriate in such cases. These patients appear to have a severe outcome with significantly lower CR rate than similar cases of Ph-positive ALL without a minor myeloid component.(ABSTRACT TRUNCATED AT 250 WORDS)