We demonstrate that Hdac1 and Hdac2 have a gene dose-dependent pro-oncogenic role in Eμ-myc tumorigenesis with a predominant role of Hdac1. Our results highlight the tumor-promoting role of Hdac1 and Hdac2 in both Eμ-myc tumorigenesis and tumor maintenance. This evidence concerns the gene HDAC2 and neoplasm.