Abstract Summary: Despite recent progress, computational tools that identify gene fusions from next-generation whole transcriptome sequencing data are often limited in accuracy and scalability. Here, we present a software package, BreakFusion that combines the strength of reference alignment followed by read-pair analysis and de novo assembly to achieve a good balance in sensitivity, specificity and computational efficiency. Availability: http://bioinformatics.mdanderson.org/main/BreakFusion Contact: [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics online