In this presentation, we would like to discuss the path followed for drug selection in the case of a pediatric patient with extensive allergies to proton pump inhibitors (PPIs). A 15-year-old male patient presented with complaints of dyspepsia and epigastric pain for over a period of 4–5 years. It is known that there was a previous fixed drug eruption described with omeprazole and widespread rashes after lansoprazole. Famotidine treatment was initiated, but the patient was unable to use the drug because he presented with rash and itching 1 hour after drug intake. On physical examination, fixed drug eruption was observed in the whole body and gluteal region. Gastroduodenoscopy was performed. Macroscopically, the corpus and antrum were hyperemic, antrum and duodenum were nodular, and bulbus was normal. Multiple biopsies were taken. He was referred to the pediatric allergy department for evaluation of possible cross-reactivities between PPIs. In addition to skin prick and intradermal tests with famotidine and ranitidine, the patient underwent skin patch tests with all available PPIs. The pathologic result of biopsies was Helicobacter pylori (HP) (+++) with Giemsa staining. Because of the cross-sensitivity between PPIs and the positivity of the allergy tests, triple HP treatment was not considered. This is an interesting case because the patient had extensive allergies to all existing PPIs, and no similar cases have been reported yet in the literature. After evaluation of allergic tests, quadruple treatment without PPI (bismuth, ranitidine, metronidazole, and tetracycline) was initiated. HP treatment was assessed after 4 weeks, and two-step monoclonal stool HP antigen test was found to be negative.