PEBP2/CBF is a heterodimeric transcription factor composed of alpha and beta subunits. Previously, we reported two distinct mouse genes, PEBP2 alpha A and PEBP2 alpha B, which encode the alpha subunit. PEBP2 alpha B is the homologue of human AML1, encoding the acute myeloid leukemia 1 protein. AML1 and human PEBP2/CBF beta were detected independently at the breakpoints of two characteristic chromosome translocations observed frequently in two subtypes of acute myeloid leukemia. The PEBP2 alpha proteins contain a 128-amino-acid (aa) region highly homologous to the Drosophila melanogaster segmentation gene runt. The evolutionarily conserved region, named the Runt domain, harbors DNA-binding and heterodimerizing activities. In this study, we identified the third Runt-domain-encoding gene, PEBP2 alpha C, which maps to 1p36.11-p36.13 in the human chromosome and encodes a 415-aa protein. PEBP2 alpha C forms a heterodimer with PEBP2 beta, binds to the PEBP2 site and transactivates transcription, similar to PEBP2 alpha A and PEBP2 alpha B.