Background: Chronic diarrhoea affects 5–10% of the adult population. Histologic lesions of possible diagnostic significance are found under normal colonoscopy in approximately 30% of patients affected by chronic diarrhoea. Mastocytic enterocolitis is characterized by an increase in the number of mucosal mast cells (MC) in the gut of patients with chronic intractable diarrhoea, detected by immunohistochemical staining, responding to mast-cell targeted drugs. The question arises whether to search for MC infiltration in specific subsets of patients as a matter of routine clinical practice. Summary: A systematic electronic search of the English literature up to December 2017 was performed, using Medline, EMBASE, Web of Science, Scopus, and the Cochrane Library. This revealed 9 studies reporting an increased number of MC in the gut mucosa of patients with chronic diarrhoea. No consensus was found, however, on the actual cutoff point, the overlap in range between patients and controls being too great to be of clinical significance. The available evidence does not therefore justify the routine evaluation of MC count. Key Messages: More studies are needed to better define MC count and the significance of MC degranulation in normal and pathological settings. Until these become available, the search for MC infiltration in specific subsets of patients should be restricted to research settings.