A significant portion of the human genome encodes genes that transcribe long non-protein coding RNAs (lncRNAs). LncRNAs participate in several biological processes, including chromatin organization and transcriptional and post-transcriptional gene expression, and act as structural scaffolds of cellular domains. Studies from our group and others have demonstrated the vital roles lncRNAs play in cancer progression by acting as oncogenes or tumor suppressor genes. In the talk, I will describe some of our work, highlighting the role of lncRNAs in gene expression control and nuclear organization during cancer progression.