<p>The purpose of the study was to determine the effectiveness of existing approaches to detect hereditary alpha-tryptasemia (HαT) and to identify key factors that affect the accuracy of differentiating this condition from other disorders associated with elevated tryptase levels. Methodologically, the work was based on a systematic literature review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, which involved critical analysis, selection, and synthesis of 62 scientific publications from 2019 to 2024, selected according to the criteria of availability of quantitative data on tryptase levels, genetic testing results and clinical symptoms. The results indicate that an increase in the number of copies of the <i>TPSAB1</i> gene can be detected in 4–6% of the population and causes a consistently elevated basal tryptase level, which is associated with both an asymptomatic course (in approximately two-thirds of patients) and pathological manifestations such as gastrointestinal disorders, anaphylaxis, and neurovegetative disorders. It was found that the determination of “background” tryptase in the dynamics allows distinguishing hereditary elevation from acute mast cell degranulation, and a comprehensive genetic study of <i>TPSAB1</i> together with the measurement of histamine, leukotrienes and prostaglandins increases the specificity of diagnosis. An important finding was that dysbiosis and related changes in intestinal barrier function can increase tryptase release and exacerbate clinical symptoms, which should be taken into account when choosing a therapeutic strategy. Given the data obtained, it was concluded that a multidisciplinary approach involving allergists, immunologists, and geneticists is needed, as well as periodic monitoring of tryptase levels. The practical significance lies in the improvement of diagnostic algorithms, which allows for earlier identification of hereditary alpha-tryptasemia and personalised management of patients.</p>