Highlights d Single endogenous EVs can be live-visualized in the zebrafish embryo with CD63-pHluorin d Syntenin in the YSL regulates exosome release into the blood for further dissemination d YSL exosomes are taken up by macrophages and endothelial cells in the tail of the embryo d Uptake is scavenger receptor-and dynamin-dependent and provides trophic support

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Graphical Abstract Highlights d MemBright allows for bright and specific staining of EVs d The zebrafish embryo allows tracking of tumor EVs at high spatiotemporal resolution d Circulating tumor EVs are mostly taken up by endothelial cells and patrolling macrophages d Zebrafish melanoma EVs favor metastatic outgrowth in zebrafish embryos