In 2003, FDA approved palonosetron as an effective drug for the control ofnausea and vomitingassociated tochemotherapy. Palonosetron is suggested in case of emetogenic chemotherapy schedules, in particular, in the case of cisplatin, high-dose cyclophosphamide, and anthracyclines. Palonosetron differs from the older 5-HT3 antagonists in its prolonged half-life (approximately 40 h) and its greater binding affinity for the 5-HT3 receptor. In three randomized prospective clinical trials, it compares favorably with the older 5-HT3 in terms of effectiveness and safety [1]. Most commonly reported adverse reactions include headache (9%) and constipation (5%). Less frequent side effects (<1%) involved cardiovascular system (tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation), gastrointestinal system (diarrhea, dyspepsia, abdominal pain, dry mouth, hiccups, and flatulence), nervous system (dizziness, somnolence, insomnia, hypersomnia, paresthesia), and alterations of hearing and vision. We report the occurrence of generalized tonic clonic seizure after i.v. palonosetron in a breast cancer patient receiving anthracycline-based chemotherapy. To our best knowledge, this side effect has never been reported in literature for this drug. A 43-year-old women with early breast cancer and no prior history of seizure was planned for CEF chemotherapy (cyclophosphamide 600 mg/m 2 , 5-FU 600 mg/m 2 , and epirubicin 90 mg/m 2 q3 wks). The antiemetic treatment consisted of 8 mg dexamethasone and 0.25 mg of palonosetron administered i.v. bolus 30 min before chemotherapy. During the fourth cycle of chemotherapy, 1 h after the antiemetic therapy while the patient was on chemotherapy with 5-FU, she developed generalized tonic clonic seizure lasting for 8 min followed by a period of drowsiness. Upon physical examination, blood pressure was 120/ 75 mmHg with pulse of 102 per minute regular; electrocardiogram and compute tomography scan of the head were normal. Her biochemical and hematological parameters were essentially normal. The patient was treated with diazepam 10 mg i.v. and saline infusion. Detailed investigations (neurological examination, electroencephalogram, Holter monitoring) failed to reveal anything abnormal and the patient was discharged after 2 days in good clinical conditions. We suspected palonosetron to be implicated in the occurrence of seizure and the patient received the following two cycles of chemotherapy with metoclopramide (20 mg i.v. every 8 h for 2 days) and dexamethasone without any problems. After excluding other causes and since an older selective 5-HT3 antagonist (i.e., ondansentron) has been reportedly associated with seizure [2, 3], we suspect palonosetron to be the one responsible for the seizure. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.