The invention provides methods of targeting tumor stem cells that comprise inhibiting the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. The invention further provides methods for identifying tumor stem cells comprising detecting increased levels and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. Further provided are kits and articles of manufacture comprising inhibitors of the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7. Methods for screening for inhibitors of the level and/or activity of HDAC1, HDAC7 and phosphorylated HDAC7 are also provided.