Here, our combined data with chemical inhibition, including the HDAC2-specific inhibitor Santacruzamate A, and genetic KO strategies show that while both HDAC1 and HDAC2 contribute to the growth characteristics of BTSCs, HDAC2 is the most relevant HDAC for growth and maintenance of stemness and tumor-initiating potential in BTSCs of different genetic backgrounds. This evidence concerns the gene HDAC2 and neoplasm.