Exosomes — nano-vesicles secreted by multiple cell types, including cancer cells, which contain proteins, mRNA and microRNAs (miRNAs) — are believed to promote tumour growth and progression. Here, Melo et al. show that exosomes derived from cancer cells and serum from patients with breast cancer contain the RNA-induced silencing complex (RISC)-loading complex proteins, Dicer, TAR RNA-binding protein 2 (TRBP) and Argonaute-2 (AGO2), and show capacity for cell-independent miRNA biogenesis. In cell culture and mice models, these cancer exosomes rapidly silence mRNAs to alter the transcriptome of recipient cells, stimulating non-tumorigenic epithelial cells to form tumours in a Dicer-dependent manner.