Nuclear chromatin structure differs dramatically between normal, precancerous, and tumor cells and is still one of the most accurate markers for cancer diagnosis. Unfortunately, the nature of chromatin structure differences between normal and tumor cells is not well defined and there have been only limited attempts to exploit these differences for cancer prevention and therapy. Nevertheless, the demonstrated anticancer efficacy of HDAC inhibitors suggests that chromatin is likely a promising source of anticancer targets. A novel class of chromatin modifying small molecules, Curaxins, with broad anticancer activity in multiple models of cancer, were recently discovered. Curaxins inhibit activity of Facilitates Chromatin Transcription (FACT) complex. FACT is involved in chromatin remodeling in tumor and stem cells and is a promising candidate marker and target of cancer. Inhibition of FACT is accompanied by changes in chromatin structure as well as activity of several cancer-related transcriptional factors, which require FACT assistance for the transcription of their target genes. The cover features an immunofluorescence photomicrograph of mammary adenocarcinoma cells treated with Curaxin-137 and stained with antibodies to NF-κB, a well-known tumor-promoting transcriptional factor. Curaxin-137 causes nuclear accumulation of inactive NF-κB which is incapable of induction of transcription in the absence of FACT. See the article by Koman et al. (beginning on page 1025) for more details about the tumor-preventive activity of Curaxin-137.