Irritation fibroma is a common hyperplastic lesion of the oral mucosa that can occur in response to chronic irritation or trauma. This report presents an unusual case of irritation fibroma associated with ectopic eruption of the maxillary left central incisor in a patient with Angelman syndrome. Considering the patient’s medical history and cooperative ability, excisional biopsy under intramuscular sedation using midazolam was performed. The patient exhibited successful healing without lesion recurrence. It is important to perform histopathological examination followed by excisional biopsy, because other benign or malignant tumors may mimic the clinical appearance of an irritation fibroma.