To analyze the development pathways of early hematopoietic cells, we studied the rearrangement and expression of the immunoglobulin (Ig) and T-cell receptor (TCR) genes in 12 patients with acute unclassified leukemia (AUL). Leukemia cells from these patients were negative for myeloperoxidase staining and failed to express B-cell, T-cell, or megakaryocyte associated antigens. The expression of the CD7 antigen, myeloid associated antigens, or both was detected in three patients each. Ig and/or TCR gene rearrangements were detected in seven of the 12 patients, and five had rearrangement of both the Ig and TCR genes. Full length mature TCR gene transcripts were not demonstrated in most of the patients showing TCR gene rearrangements. In contrast, cells from two patients with germline configurations of the Ig and TCR genes tested expressed truncated forms of both Ig and TCR genes. These results suggest that AUL may generally originate from undifferentiated cells with an aberrant rearrangement and/or expression of the Ig and TCR genes.