Ten cases of adult acute myeloid leukemia (AML) displaying lymphoid-associated markers CD7 and/or terminal deoxynucleotidyl transferase (TdT) have been investigated for rearrangement of immunoglobulin and T cell antigen receptor beta and gamma genes. Two of six TdT+ cases had clonally rearranged Ig genes, whereas six of eight CD7+ AMLs, including three that were TdT+, had a germ line configuration of both immunoglobulin and T cell receptor beta and gamma genes. A single case of CD7+ TdT- AML had clonal rearrangement of all three genes. These results indicate that expression of TdT and/or CD7 is not accompanied by gene rearrangement in most cases of adult AML. A minority of cases, displaying lymphoid-associated phenotypic markers and accompanying gene rearrangement, may represent a distinct subgroup of AML that arises from a rare, primitive stem cell, possessing extensive multilineage potential.