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We report the case of a 68-year-old patient with diagnosed systemic mastocytosis and histopathologically confirmed manifestations in the stomach and intestinal tract who underwent 18F-Fluorodeoxyglucose ([18F]FDG) positron-emission tomography/computed tomography (PET/CT) pre- and post-6-month therapy with midostaurin, an established tyrosine kinase inhibitor. Post-therapeutic [18F]FDG PET/CT showed decreased multifocal tracer uptake in the known lesions in the gastrointestinal tract, which was consistent with relief of the patient’s symptoms and decrease in serum tryptase level. [18F]FDG PET/CT may thus be considered a potential method for monitoring the outcome of midostaurin therapy in systemic mastocytosis.