Dan Robinson and colleagues used pair-end transcriptome sequencing to examine gene fusions in breast cancer cell lines and tumours. Among the expressed gene fusions they found five microtubule-associated serine-threonine (MAST) kinase fusions and eight NOTCH fusions. Expression of the MAST gene fusions in benign breast epithelial cells increased proliferation, and small interfering RNAs targeted against MAST2 in cell lines expressing a ARID1A–MAST2 fusion gene reduced growth and viability in vitro. Similar experiments overexpressing NOTCH1 and NOTCH2 fusion proteins in benign breast epithelial cells resulted in altered growth characteristics, such as anchorage independence. In addition, the inhibition of NOTCH signalling reduced the growth of NOTCH gene fusion-expressing breast cancer xenografts. These findings indicate that transcriptome analyses could identify patients with breast cancer who harbour rare gene fusions that are therapeutically relevant.