The protein-coding regions of mRNAs have the information to make proteins and hence have been at the center of attention for understanding altered protein functions in disease states, including cancer. Indeed, the discovery of genomic alterations and driver mutations that change protein levels and/or activity has been pivotal in our understanding of cancer biology. However, to better understand complex molecular mechanisms that are deregulated in cancers, we also need to look at non-coding parts of mRNAs, including 3 ' UTRs (untranslated regions), which control mRNA stability, localization, and translation efficiency. Recently, these rather overlooked regions of mRNAs are gaining attention as mounting evidence provides functional links between 3 ' UTRs, protein functions, and cancer-related molecular mechanisms. Here, roles of 3 ' UTRs in cancer biology and mechanisms that result in cancer-specific 3 '-end isoform variants will be reviewed. An increased appreciation of 3 ' UTRs may help the discovery of new ways to explain as of yet unknown oncogene activation and tumor suppressor inactivation cases in cancers, and provide new avenues for diagnostic and therapeutic applications.