Here, we discuss the intricate relationship between alternative splicing and signalling at different levels: (i) how the activity of components in the Ras-MAPK signalling pathway is regulated by alternative splicing in cancer cells; (ii) how the activity of components in the PI3K-mTOR pathway is regulated by alternative splicing in cancer cells; (iii) mechanisms by which extracellular stimuli can be communicated to the splicing machinery and to specific RNA-binding proteins that ultimately control exon definition events. Here, PTBP1 is linked to cancer.