BACKGROUND Adverse reaction to histamine found in food and beverages is still a debated entity. It presents with a diverse, multisystemic clinical picture and lacks objective diagnostic criteria. CASE REPORT We report a case of severe adverse reaction to histamine in food and beverages. The 36-year-old White man had diet-dependent problems for 17 years that involved periodic erythematous rash, fever, headaches, nausea, and upper respiratory symptoms. The symptoms developed in the same chronologic order each time. The course of the disease could be divided into a first (prodromal, gastrointestinal), a second (acute, dermal), and a third (subacute, respiratory) phase. The symptoms occurred every 3-6 weeks and lasted for 10-14 days. The differential diagnosis was time-consuming and very detailed. Family history, genetic testing, and oral histamine provocation testing supported the diagnosis of an adverse reaction to histamine in food and beverages. A low-histamine diet resulted in a symptom-free state. Follow-up lasted longer than 24 months. CONCLUSIONS This presentation of an adverse reaction to histamine in food and beverages can serve as a textbook example where a chronological, syndrome-like order of symptom appearance is described. To the best of our knowledge, this is the first report of a severe adverse reaction to histamine in food and beverages, where symptoms are described in 3 distinct recurring phases.