Abstract: Long non-coding RNAs (lincRNAs), a relatively recently recognized class of widely transcribed genes, are thought to affect chromatin state and epigenetic regulation, but their mechanisms of action and potential roles in human disease are poorly understood. The present invention shows that long non-coding RNAs in the human HOX loci are systematically dysregulated during breast cancer progression, and that expression levels of the lincRNA termed HOTAIR can predict cancer metastasis. Elevated levels of HOTAIR can lead to altered patterns of Polycomb binding to the genome. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.