Background:Systemic mastocytosis (SM) is a rare clonal hematologic disorder primarily driven by the KIT D816V mutation in almost all (95%) patients. These patients most often have elevated serum tryptase levels and can present with a wide spectrum of symptoms caused by mediator release from clonal mast cell degranulation (e.g., skin rash, anaphylaxis, diarrhea, and neurocognitive symptoms). However, these symptoms are similar in other non-clonal mast cell disorders such as idiopathic mast cell activation syndrome (MCAS) and hereditary alpha-tryptasemia (HaT). As such, many patients are referred to hematology for SM work-up based on elevated serum tryptase and mediator release symptoms. We evaluated a real-world single-center experience determining whether elevated serum tryptase, mediator release symptoms, and/or a history of anaphylaxis correlated with a diagnosis of SM.