The appendix is a worm-like, blind-ending tube, with its base on the caecum and its tip in multiple locations. Against all odds, it plays a key role in the digestive immune system and appendectomy should therefore be cautiously considered and indicated. We report the case of a 45-year-old male with a known history of Fragile-X syndrome who presented to the emergency department with intense abdominal pain and was suspected of acute appendicitis, after a positive Dieulafoy’s triad was confirmed. The laparoscopic exploration showed no signs of inflammation of the appendix; nonetheless, its removal was carried out. Rising inflammatory laboratory parameters led to a focused identification of a pleural empyema due to a tooth inlay aspiration. Our objective is to emphasize the importance of a thorough anamnesis, even in cases of mentally impaired patients, as well as to highlight a rare differential diagnosis for appendicitis. Acute appendicitis is an emergency condition that requires a thorough assessment and appropriate therapy. Clinical examinations are important, but in this particular case, imaging methods had a much more important role in establishing the right treatment approach. Furthermore, the signs of acute appendicitis are mimicked by several medical conditions including respiratory tract infections.