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To analyse the association of systemic allergic hymenoptera sting reactions with mastocytosis and elevated baseline serum tryptase and to discuss diagnosis and treatment in patients with both diseases.In recent large studies on patients with mastocytosis a much higher incidence of severe anaphylaxis following hymenoptera stings than in the normal population was documented. In patients with hymenoptera venom allergy, elevated baseline tryptase is strongly associated with severe anaphylaxis. Fatal sting reactions were reported in patients with mastocytosis, notably after stopping venom immunotherapy. During venom immunotherapy most patients with mastocytosis are protected from further sting reactions. Based on these observations immunotherapy for life is recommended for patients with mastocytosis and venom allergy. The incidence of allergic side-effects is increased in patients with mastocytosis and elevated baseline tryptase, especially in those allergic to Vespula venom. Premedication with antihistamines, or omalizumab in cases with recurrent severe side-effects, can be helpful.In all patients with anaphylaxis following hymenoptera stings, baseline serum tryptase should be determined. A value above 11.4 μg/l is often due to mastocytosis and indicates a high risk of very severe anaphylaxis following re-stings. Venom immunotherapy is safe and effective in this situation.