How aneuploidy leads to aberrant cellular and organismal phenotypes remains poorly understood, although a transcriptional signature that is characteristic of a stress response has been seen in aneuploid yeast and mouse cells. In this study, the authors analysed a large collection of gene expression data from aneuploid cells from diverse organisms. This revealed that transcriptional changes associated with stress and decreased proliferation occur across species and are largely independent of the identity of the aneuploid chromosome. Thus, eukaryotic cells seem to have a generic response to a chromosome-scale gene dosage change.