BACKGROUND: Indolent systemic mastocytosis (ISM) without skin lesions (ISMs-) shows a higher prevalence in males, lower serum baseline tryptase levels, and KIT mutation more frequently restricted to bone marrow (BM) mast cells (MCs) than ISM with skin lesions (ISMs+). Interestingly, in almost one-half of ISMs- patients, MC-mediator release episodes are triggered exclusively by insects. OBJECTIVE: We aimed to determine the clinical and laboratory features of ISMs- associated with insect-induced anaphylaxis (insectISMs-) versus other patients with ISM. METHODS: A total of 335 patients presenting with MC activation syndrome, including 143 insectISMs-, 72 ISMs- triggered by other factors (otherISMs-), 56 ISMs+, and 64 nonclonal MC activation syndrome, were studied. RESULTS: Compared with otherISMs- and ISMs+ patients, insectISMs- cases showed marked male predominance (78% vs 53% and 46%; P