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Systemic mastocystosis, a disorder of clonal mast cell expansion presents with symptoms of flushing, pruritus, musculoskeletal pain, gastrointestinal cramping and vascular instability. Patients with neuroendocrine tumors may present with similar symptoms due to the release of vasoactive mediators in both diseases. We report the co-occurrence of systemic mastocytosis and a neuroendocrine pancreatic tumor for which the patient received disease-specific treatment.