Alternative splicing is a fundamental mechanism to modulate gene expression programs in response to different growth and environmental stimuli. There is now ample evidence that alternative splicing errors, caused by mutations in cis-acting elements and defects and/or imbalances in trans-acting factors, may be causatively associated to cancer progression. Recent work indicates the existence of an intricate network of interactions between alternative splicing events and signal transduction pathways. In this network, splicing factors occupy a central position and appear to function both as targets and effectors of regulatory circuits. Thus, a change in their activity deeply affects alternative splicing profiles and hence the cell behavior. Here, we discuss a number of cases that exemplify the involvement of deregulated alternative splicing in tumor progression.