On the basis of the currently available evidence, we suggest that depending on spatiotemporal conditions that are linked to tumor angiogenesis within the tumor microenvironment, extracellular HSP70-1A secreted from tumor cells may specifically bind to CLEC14a expressed on tumor vessels via a specific region (amino acids 43–69) of CLEC14a-CTLD to promote CLEC14a-CTLD-mediated endothelial cell-cell contacts and stimulate angiogenic functions. The gene discussed is HSPA1A; the disease is neoplasm.