The translocation (6;9) in acute nonlymphocytic leukemia results in the formation of a dek-can fusion gene. In a case of acute undifferentiated leukemia, the oncogene can is fused to a different gene, named set, instead of dek and is assumed to be activated. Transcripts of set encode a putative SET protein with a predicted molecular mass of 32 kDa. We identified SET as a 39-kDa protein by immunoprecipitation with rabbit antiserum against each of three synthetic peptides predicted from the open reading frame of the set gene. We confirmed this identification of SET by protein sequencing. We also observed that SET is expressed ubiquitously in various human cell lines. SET is phosphorylated on serine residue(s) in cultured cells and is localized predominantly in nuclei. Although the function(s) of SET and SET-CAN is not known, we propose that SET plays a key role in the mechanism of leukemogenesis in acute undifferentiated leukemia, perhaps by activating CAN in nuclei and stimulating the transformation potential of SET-CAN. This proposed role would therefore be similar to the roles observed for BCR and DEK of the chimeric oncoproteins BCR-ABL and DEK-CAN in acute myeloid leukemia and acute nonlymphocytic leukemia, respectively.