Although altered mitochondrial function is a feature of tumour cells, not many somatic mutations in the mitochondrial genome have been characterized. Stewart et al. used both genomic and transcriptomic sequencing data from 527 tumour samples from 14 different cancer types to reveal imbalances that arise when genetic alleles are differentially transcribed or processed. They have identified 15 somatic mitochondrial DNA (mtDNA) mutations that occur mostly in transfer RNA (tRNA) genes and are associated with strong accumulation of immature tRNA precursors, indicating impaired tRNA maturation in cancer. They also found that tRNA secondary structure is needed for correct maturation. As processing of specific tRNAs by cleaving at tRNA boundaries is a key step to convert mitochondrial large polycistronic RNAs into smaller gene products, the authors found that mutations affecting tRNA folding can impair maturation of not only the affected tRNA but also neighbouring gene transcripts.