Distinct isoforms of the Mena protein are expressed in invasive and migratory tumour cells in vivo. Mena invasive (MenaINV) potentiates carcinoma-cell metastasis, but the stage of metastasis that MenaINV targets has remained unknown. Here, the laboratories of Doug Lauffenburger, Frank Gertler and John Condeelis (p. 2120) characterise the metastatic cascade affected by MenaINV, and determine the impact of a second regulated isoform, Mena11a, on metastatic progression. Using multiphoton-based intravital imaging of MTLn3 mammary tumour cells, the authors reveal a new form of collective cell migration that they term ‘streaming motility’, in which cells move in an ordered single-file line. MenaINV increases streaming motility and also enhances transendothelial migration and intravasation of tumour cells. These processes are dependent on paracrine signalling between MenaINV-expressing tumour cells and macrophages. In contrast to MenaINV, Mena11a expression correlates with decreased cell streaming and a dramatically reduced ability to participate in paracrine-mediated invasion and intravasation; paracrine-mediated cell streaming and intravasation are therefore important for tumour-cell dissemination. The authors conclude that the relative levels of MenaINV and Mena11a are key for the regulation of invasion, migration and intravasation, which are all crucial stages in the metastatic progression of breast cancer cells.