Background: Horner syndrome is a rare but likely underdiagnosed complication of internal jugular vein cannulation. Case report: We present a case of a young woman undergoing chemotherapy for gestational trophoblastic disease for whom venous port implantation was attempted due to poor peripheral vein access. Despite ultrasound guidance, the procedure was unsuccessful and complicated by a local haematoma, causing compression of the sympathetic nerves with Horner syndrome. The symptoms subsided within 3 weeks without treatment. The possible pathomechanisms of Horner syndrome after central venous cannulation are presented with suggested diagnostic and therapeutic approaches. Special emphasis must be placed on excluding carotid artery dissection because it carries the risk of subsequent cerebral vascular incidents. In the event of a carotid dissection, a multidisciplinary team must choose a pharmacological (antiplatelet drugs/anticoagulation) or interventional approach. Conclusion: Even with ultrasonography, central venous cannulation is not free of serious risks. In case of anisocoria following an uneventful procedure, diagnostic imaging of the vascular structures in the neck is mandatory for the exclusion of potentially serious complications, such as carotid dissection or venous thrombosis.