CCAAT/enhancer binding proteins (C/EBPs) are a family of transcription factors that have been implicated in diverse cellular functions such as cellular differentiation and proliferation, and inflammatory processes. C/EBPzeta, also known as GADD153, CHOP10, and DDIT3 has been found associated with the development of myxoid liposarcoma and the progression of melanoma. To investigate the correlation of C/EBPzeta transcript levels with the development of leukemia, samples from 187 patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML) were examined for C/EBPzeta mRNA using real-time quantitative PCR (RQ-PCR). RQ-PCR analysis demonstrated the median levels of C/EBPzeta were significantly decreased in MDS, AML, and CML patients compared with normal controls (1.40, 0.96, 2.60 versus 14.69, P<0.0001). Significant differences were also observed between patients with CML and with AML or MDS. These results suggest that the insufficient dosage of C/EBPzeta might be involved in the development of leukemia.