Abstract Background Peanut and soybean allergies are listed as contraindication in the package leaflet of isotretinoin, a widely used treatment of acne vulgaris. Cross-reactivity between PR10-proteins in peanut, tree nuts, and soybean is particularly common in patients with birch pollinosis and may lead to anaphylactic reactions in sensitized patients after intake of soybean oil containing isotretinoin capsules. Case presentation Here, we describe a young man with hazelnut and birch pollen allergy, who experienced exercise-induced anaphylaxis after isotretinoin intake on the third day of treatment. A complete allergy work-up was carried out, and sensitization to both peanut and soybean PR10-proteins was confirmed. However, oral provocation with isotretinoin remained negative in the absence of intense physical activity and longterm treatment was well tolerated. Conclusion To our knowledge, this is the first report of an exercise-induced anaphylaxis due to isotretinoin therapy. Our literature review to assess tolerability of isotretinoin in patients allergic to peanut, tree nuts or soybean revealed only one other case of anaphylaxis in a cashew-nut allergic patient sensitized to soybean PR10-protein Gly m 4. While there are no reports on soybean allergic patients treated with isotretinoin, the vast majority of peanut or tree nut allergic patients tolerated isotretinoin. Therefore, we conclude that sensitization to soybean, peanut or tree nuts should not preclude isotretinoin therapy. Particular caution is however warranted in patients with soybean sensitization. Pre-treatment oral challenges with isotretinoin may be recommended and physicians should be aware of the potential role of cofactors.