Endosialin (TEM-1, CD248) is a transmembrane glycoprotein belonging to the C-type lectin domain family. It is highly expressed on pericytes and cancer-associated fibroblasts (CAFs) in the tumor stroma, as well as on some tumor cells, but is largely absent in normal adult tissues. Endosialin interacts with extracellular matrix components (e.g., fibronectin, collagen) and modulates cell adhesion, migration, and matrix organization. In oncology, its expression correlates with tumor progression, metastasis, and poor prognosis, likely by supporting tumor angiogenesis and creating a permissive stromal microenvironment. Therefore, endosialin represents a promising stromal target for antibody-based therapies aimed at disrupting the tumor-stroma interaction.