One of the most used cephalosporins in clinical practice is cefuroxime axetil. Anaphylaxis due to the administration of cefuroxime is considered a rare event. We report a case of anaphylactic reaction after the administration of cefuroxime in a child who had tolerated the drug in past exposures. Diagnostic workup is recommended for all patients with at least a moderate anaphylactic reaction (hypotension, tachycardia, bronchial hyperreactivity). This should include a detailed history of the event, previous allergies, and underlying conditions. Unfortunately, all currently available diagnostic approaches (IgE, skin-prick-test, tryptase) leave a significant percentage of non-diagnostic results and false positive or negative outcomes.