We used representational difference analysis to discover new genes with specific expression in dendritic cells. Among other genes, we identified HEP27, encoding a member of the short chain alcohol dehydrogenase/reductase family to be upregulated during monocyte to dendritic cell differentiation. Originally cloned from hepatocellular carcinoma cells (HepG2), HEP27 was exclusively expressed in monocyte-derived dendritic cells within the hematopoietic system. The presence of different transcripts in monocyte-derived dendritic cells, HepG2 cells, and various tissues could be traced back to alternative splicing and alternative promoter usage. We describe here the complete genomic organization of HEP27, including two alternative promoter regions: a hepatocyte-specific promoter which was induced by the histone deacetylase inhibitor sodium butyrate in several other cell types, and a second upstream promoter which was specifically active in monocyte-derived dendritic cells. Its exclusive usage in monocyte-derived dendritic cells makes the alternative HEP27 promoter an interesting target to study dendritic-cell-specific gene regulation.