Using RNA sequencing (RNA-seq), Scott et al. discovered a novel recurrent gene fusion between TBL1XR1 and TP63 in diffuse large B-cell lymphoma (DLBCL). Further analysis revealed the TBL1XR1/TP63 fusion was exclusive to DLBCL derived from germinal center B-cells. TBL1XR1 encodes a component of the NCoR/SMRT transcription repressor complex, and TP63 encodes a protein that is part of the TP53 family of transcription factors. These results demonstrate how RNA-seq is helping to reveal previously unidentified gene fusions in various cancers.