BACKGROUND: Serum tryptase levels are used as a diagnostic marker in mastocytosis and are considered an indicator of clonal mast cell load. AIM: To analyze tryptase levels in children with different clinical types of cutaneous mastocytosis. MATERIALS AND METHODS: A single-center prospective study was conducted for the period 2022–2024. The results of examination of 202 children aged from 6 months to 17 years with a diagnosis of cutaneous mastocytosis, who were undergoing outpatient treatment at the Moscow scientific and practical Center of dermatovenereology and cosmetology, were analyzed. Serum tryptase levels were determined by enzyme immunoassay. RESULTS: The median basal tryptase level for the entire group (n=202) was 5.09 μg/L (range 1.3–57.0 μg/L). Serum tryptase values exceeding 11.0 μg/L were detected in 17.3% of patients, and 20.0 μg/L in 7.4%. The mean enzyme level in the control group was 2.55 μg/L. There were significant differences in tryptase concentrations between the maculopapular cutaneous mastocytosis and control groups (p=0.05). The median tryptase level in children with maculopapular cutaneous mastocytosis was 8.7 μg/L. The most pronounced differences were observed between the enzyme levels in children with the monomorphic type of maculopapular cutaneous mastocytosis and in the control group (p=0.01). Analysis of tryptase levels depending on gender and clinical type of maculopapular cutaneous mastocytosis showed that children and adolescents with the monomorphic type of maculopapular cutaneous mastocytosis had higher enzyme levels. CONCLUSION: Further studies are needed to determine which tryptase levels in children are indicative of mast cell activation and primary mast cell diseases. A detailed understanding of tryptase levels in children may facilitate the development of new specific therapeutic approaches to the management of various clinical forms of cutaneous mastocytosis. © 2024 Elsevier B.V., All rights reserved.