Telomeres are the ends of chromosomes and protect them from degradation and fusion. As such, their stability is required for normal cellular function. Telomere dysfunction is found often at the origin of cellular transformation and contributes to the onset of genomic instability, a hallmark of cancer cells. In this article, I discuss current data and concepts on telomere-mediated chromosomal rearrangements in cancer. J. Cell. Biochem. 109: 1095–1102, 2010. © 2010 Wiley-Liss, Inc.