STC1 is a protein secreted by intratumor endothelial cells in which plasma concentrations increase in patients with chemorefractory mCRC. Based on analyses of patients with refractory mCRC in the TEXCAN and CORRECT trials, we found that STC1 plasma levels had a prognostic role for OS, with high levels associated with poor outcome. A predictive role for baseline STC1 levels was pointed out for regorafenib efficacy.