Through lateral transfer, extra-cellular vesicles (EVs) transport their DNA, miRNA, mRNA and proteins such as enzymes mediating drug resistance, transporters as well as growth factors to neighboring cells. By virtue of this horizontal transfer, EVs potentially regulate cell growth, migration, angiogenesis and metastasis and increase tissue permeability in cancer. Furthermore, EVs regulate immune factors and allow the tumor cells to evade immune recognition and cell death. To explore if the proteomes of exosomes support functional transfer of cancer hallmarks, in this meta-analysis, we compared EVs and whole cell proteomes from the NCI-60 human tumor cell line panel. We observed a subgroup of proteins in each cancer hallmark signature as highly abundant and consistently expressed in EVs from all cell lines. Among these were oncoproteins frequently targeted in cancer therapies whose presence on EVs could potentially render therapies less effective by serving as decoys.