mRNA 3'-end processing involves the addition of a poly(A) tail based on the recognition of the poly(A) signal and subsequent cleavage of the mRNA at the poly(A) site. Alternative polyadenylation (APA) is emerging as a novel mechanism of gene expression regulation in normal and in disease states. APA results from the recognition of less canonical proximal or distal poly(A) signals leading to changes in the 3' untranslated region (UTR) lengths and even in some cases changes in the coding sequence of the distal part of the transcript. Consequently, RNA-binding proteins and/or microRNAs may differentially bind to shorter or longer isoforms. These changes may eventually alter the stability, localization, and/or translational efficiency of the mRNAs. Overall, the 3' UTRs are gaining more attention as they possess a significant posttranscriptional regulation potential guided by APA, microRNAs, and RNA-binding proteins. Here we provide an overview of the recent developments in the APA field in connection with cancer as a potential oncogene activator and/or tumor suppressor silencing mechanism. A better understanding of the extent and significance of APA deregulation will pave the way to possible new developments to utilize the APA machinery and its downstream effects in cancer cells for diagnostic and therapeutic applications.