By analysing the phenotype of circulating tumour cells in the bone marrow of patients with early-disseminated breast cancer, Werner et al. have shown that dissemination might be driven by low levels of retinoic acid-induced 2 (RAI2). Depletion of RAI2 in luminal breast cancer cell lines resulted in dedifferentiation and increased invasiveness. RAI2 interacts with C-terminal-binding proteins (CTBPs), which control the expression of target genes involved in breast cancer. These results suggest that RAI2 maintains differentiation of luminal breast epithelial cells and might prevent metastasis initiation.