Relying on a panel of systemic mastocytosis (SM) patient-specific iPS cell lines carrying the <i>KIT</i> D816V mutation, we generated functional MCs that recapitulate SM disease features: increased number of MCs, abnormal maturation kinetics and activated phenotype, CD25 and CD30 surface expression and a transcriptional signature characterized by upregulated expression of innate and inflammatory response genes. The gene discussed is KIT; the disease is systemic mastocytosis.