Glioblastoma (GBM) is the most aggressive brain tumor, with aberrant angiogenesis driving its progression. This study explored the angiogenic properties of patient-derived glioma stem cells (GSCs) and assessed galectin-1 (Gal1) as a therapeutic target. Four GSC lines (G02, G03, G08, G09) were analyzed by transcriptomics and functional assays, revealing marked heterogeneity. G02 showed an endothelial-like transcriptomic profile and enhanced endothelial migration, though lacked protein expression after transdifferentiation. G03 displayed enrichment of angiogenesis pathways, microvascular proliferation in patient biopsies, and superior tube formation ability. All GSCs formed tube-like structures, with G03 being most efficient. Gal1, a lectin involved in migration, proliferation, and angiogenesis, emerged as a differential target. Blocking Gal1 or VEGF reduced tube formation in G03, while Gal1 silencing also impaired G02. Findings highlight Gal1’s extracellular and intracellular roles and the variable angiogenic potential of GSCs, supporting selective, personalized anti-angiogenic strategies in GBM to improve treatment efficacy and avoid resistance.