There are very few reports on allergic reactions to lychee fruit in the literature. We describe the case of a 26-year-old man who developed pruritus, generalized urticaria, and severe angioedema of his lips and tongue with dyspnea within 15 minutes after lychee fruit intake. Although we found no lychee-specific immunoglobulin E antibodies, a basophil activation test (BAT) and a cellular antigen stimulation test (CAST) to lychee were both positive, as was a prick-to-prick test with fresh lychee fruit. The patient also suffered from an oral food allergy syndrome to parsley and was sensitized to mugwort but not to latex or profilin. BAT and CAST are helpful tools in the diagnostic workup for exotic food allergy. Mugwort is suggested as the allergen responsible for,the cross-reactivity presented by this patient, as he had no sensitization to latex or profilin.