Aphthae are common oral lesions that affect approximately 10% to 20% of the population. Recurrent Aphthous Ulcers (RAU) are usually classified into three different types: minor, major and herptiform RAU. The etiology of aphthous stomatitis is unknown but according to increasing evidence, its development has an immunogenic process that causes the ulceration of the involved oral mucosa. Similar-appearing lesions may arise in following systemic disorders: 1. Behcet’s disease 2. Sweet’s syndrome 3. Cyclic neutropenia 4. Benign familial neutropenia 5. MAGIC syndrome 6. A periodic syndrome with fever and pharyngitis 7. Various nutritional deficiencies with or without underlying gastrointestinal disorders Several studies from the UK, United States, and Spain have demonstrated that hematinic deficiency (iron, folic acid, or vitamin B12) are twice as common in RAS patients than incontrols. Case report: A 10 year old male patient presented a 3-year history of episodes of multiple minor recurrent Ulcers, this year major aphthae on the anterior ventral surface of the soft palate. Patient had difficulty in eating and in speech. Clinical examination revealed multiple symptomatic ulcers with a perilesional erythematous halo covered with a pseudomembrane. The size of major aphthae was than 20 mm in diameter. The ulcers were not associated with any type of discharge. The ulcers were tender on palpation. The medical history and the family history were non-contributory. A clinical diagnosis of major aphthous ulcers was made on the basis of the history and the clinical examinations. The patient was subjected to a therapeutic regimen consisting of daily topical application of Prednizoloni 0.05%, topical lidoksor and systemic vitamin and Cefatoxime Natrii, Immunomodulators Biferon, Amphotericin B. Recurrent aphthous stomatitis (RAS) or recurrent aphthous ulcers (RAU) remains a common oral mucosal disorder in most communities of the world. Proper systemic evaluation is important before prescribing the medication.