Transcription factors play a key role in controlling the cellular differentiation of hematopoietic cells. Among the known transcription factors, both GATA-1 and SCL play roles in the cellular differentiation of erythrocytic and megakaryocytic lineages, while GATA-2 is thought to maintain and promote the proliferation of early hematopoietic progenitors. In this review, the clinical implications of expression of the GATA family, SCL, and EVI1 gene in various types of human leukemia are discussed. De novo acute myeloid leukemia (AML) patients may be subdivided into three categories depending on the expression pattern of transcription factors, i.e., GATA-1(+)SCL(+), GATA-1(+)SCL(-), and GATA-1(-)SCL(-). AML patients with both GATA-1 and SCL expression have a poor prognosis and have some characteristic clinical and hematologic features. The EVI1 gene may be expressed through at least two pathways in hematologic malignancies; one is related to chromosomal changes at 3q26, while the other is related to myelodysplasia regardless of chromosomal changes at 3q26 region. These findings suggest that the pattern of expression in transcription factors in abnormal hematopoietic cells is reflected in the malignant phenotype and play a role in the pathogenesis of the disease.