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This is a case of mastocytic enterocolitis in a patient with a longstanding history of suspected diarrhoea-predominant irritable bowel syndrome (IBS-D).A female patient in her 60s presents with a history of frequent diarrhoea with faecal urgency for several years. She underwent colonoscopy with gastrointestinal biopsies and immunohistochemical staining for CD117, demonstrating mast cell infiltration. The patient was diagnosed with mastocytic enterocolitis as she did not have symptoms or other findings suggesting systemic mastocytosis. Management with cromolyn sodium prior to meals was ineffective. Alternatively, management with H1 and H2 antihistamines and prebiotics provided significant clinical symptom improvement. In patients with refractory IBS-D, biopsies with immunohistochemical staining for mast cells should be considered. Prebiotic and probiotic supplementation, separately or combined, should also be considered and has not been previously described in the management of mastocytic enterocolitis.