A raised baseline serum tryptase is a risk indicator for anaphylactic reactions, especially in patients with hymenoptera venom allergy. Borderline elevations (> 11.4 μg/l) occur frequently and may necessitate invasive diagnostic procedures to rule out systemic mastocytosis. We retrospectively analysed 1,092 non-mastocytotic patients from our general dermatology clinic with respect to age- and gender-associated effects and investigated the impact of heterophilic antibody interference on the tryptase assay. The results were stratified by gender and five age classes. Sera with raised tryptase (n = 106) were re-tested after pre-incubation with Heterophilic Blocking Tubes (HBT(®), Scantibodies Laboratory; Santee, CA, USA). A significant increase in baseline tryptase was observed with increasing age. Incubation with HBT(®) caused a decline of more than 50% in only one case. In conclusion, older patients showed significantly higher serum tryptase levels and heterophilic interference was of subordinate relevance.