Mastocytosis represents a group of rare and diverse neoplasms characterized by the abnormal accumulation of mast cells in various organs or tissues. This condition is typically driven by the constitutive activation of the KIT receptor. The established classification recognizes three distinct disease types: systemic mastocytosis (SM), cutaneous mastocytosis (CM), and mast cell sarcoma (MCS). The clinical presentation of mastocytosis is heterogeneous, spanning from skin-limited disease, particularly evident in pediatric cases of cutaneous mastocytosis, where onset commonly occurs within the first 2 years of life. In contrast, a more aggressive variant with extracutaneous involvement (systemic mastocytosis) is observed in adult patients, potentially associated with multi-organ dysfunction/failure and shortened survival. Systemic mastocytosis should be distinguished from nonclonal mast cell activation syndrome (MCAS), wherein patients manifest recurrent symptoms of systemic mast cell activation with varying severity, accompanied by an increase in mast cell mediator release. Hereditary α-tryptasemia is a condition linked to an increased copy number of the TPSAB1 gene and elevated baseline serum tryptase levels, observed in both MCAS and in systemic mastocytosis.