One of the characteristic trademarks of tumorigenesis is the need for an extensive vascular system to supply blood for the tumor to grow and disseminate from the original node to distant sites via the process of metastasis. This involves the growth of new vessels from existing vessels, as well as the migration of tumor cells through the extracellular matrix (ECM) and into the lymphatic or vascular systems. However, some very aggressive solid tumors can form vascular channels by themselves, which is termed vascular mimicry (VM). Moreover, only certain cells in these tumors have the ability to produce blood-transporting channels, contributing to metastasis. There is growing evidence that supports the idea that VM can be a prognostic factor for poor clinical outcomes in various types of cancer. Currently, VM is identified by a pathologist’s evaluation of histological slides, wherein vascular-like structures that do not stain positive for endothelial cells are identified as VM. Thus far, conserved molecular biomarkers that define this phenotype have remained unknown.