The T-cell receptor gamma chain (TcR gamma) gene is rearranged in early T-cell differentiation. However, rearrangement of the TcR gamma gene is not specific for T lineage since it has also been noted in B-cell neoplasia. TcR beta gene rearrangement and heavy chain immunoglobulin gene rearrangement have also been reported in acute myelogenous leukemia (AML). Because of the previous reports of lineage heterogeneity at the molecular level, we analyzed seven patients who met the standard criteria for AML by Southern blot hybridization with a TcR gamma gene probe, a TcR beta gene probe, and an immunoglobulin heavy chain JH gene probe. In two samples, the TcR gamma gene was rearranged. One of these two samples also had rearrangement of the immunoglobulin JH gene. None of the seven samples showed TcR beta gene rearrangement. The two samples with TcR gamma gene rearrangement also showed 25% and 80% of terminal deoxynucleotidyl transferase (TdT) positivity, respectively. Both samples expressed myeloid lineage-associated antigens without any lymphoid lineage-associated antigens. Our studies indicate that TcR gamma gene rearrangement is not specific for lymphoid lineage and the presence of TcR gamma and immunoglobulin JH gene rearrangements without expression of lymphoid lineage-associated markers supports the concept that there is lymphoid lineage prematurity in AML.