The generation of new blood vessels (angiogenesis) is an essential requirement for cancer cells survival and cancer progression. Therefore, one of the therapeutic routes quests for anticancer agents able to block this phenomenon. Fucoidan seems to be a promising natural-origin alternative to current cancer chemotherapeutics. However, a previous work demonstrated that different fucoidan extracts may present disparate biological responses based on their chemical features. Considering that the angiogenic potential of fucoidan is still controversial, since both pro- and anti-angiogenic responses have been reported in literature, an effective anticancer extract was herein tested. Cytotoxicity results set 0.5 mg/mL as the selective fucoidan concentration (toxic over human breast cancer but not over endothelial cells) to be further explored while evaluating angiogenesis in vitro (tube formation assay) and in vivo (chicken embryo chorioallantoic membrane – CAM – assay). Tube formation assay demonstrated that fucoidan, either administered while endothelial cells seeding or after their adhesion, inhibited or disrupted the formation of tubular-like structures. Furthermore, fucoidan did not significantly reduced VEGF secretion, but significantly reduced the expression of PDGF when compared to the control condition (without fucoidan). Therefore, in the presence of the effective anticancer fucoidan extract, endothelial cells are metabolic active and expressing VEGF, despite not capable of forming mature tubular-like structures. To evaluate the fucoidan activity in an in vivo angiogenesis model, a multicellular tumor spheroid was onplanted into the CAM. Although the number of blood vessels seems to not be affected in vivo, the size of the tumors significantly decreased in the presence of fucoidan.