There is evidence that cancer-derived extracellular vesicles (EVs) have nearby and distant effects in the body. In order to reach distant sites, EVs need to travel through the blood stream and organs where they encounter a hostile environment in the form or phagocytic cells. However, the stability and homeostasis in the blood circulation and in the tumor microenvironment are not well understood. Phagocytosis is an important mechanism for the clearance of apoptotic and necrotic cells. As exosomes (small EV) express “eat-me” signals such as phosphatidyl-serine, it is likely that they are cleared similar to dead cells. Here we discuss measures that cancer cells have developed to protect their EVs from rapid depletion. The expression of “don’t eat me” signals such as CD47 and CD24 on the tumor cell surface and in released exosomes is of vital importance. We will focus on the role of the CD24-Siglec-10 binding axis as a stop signal at the interface between tumor cells and phagocytic cells. Extending the lifetime of EVs is essential for the cancer to achieve systemic immune suppression and to prepare metastatic niches for spreading. Keywords: CD24, CD47, Extracellular vesicles, Siglecs, carbohydrates, phagocytosis