Mastocytosis is a rare and underdiagnosed disorder characterized by mast cell proliferation in the tissues and organs of the body. The gastrointestinal manifestations of the disease can be noted in approximately 70%–80% of those patients diagnosed with the disorder. Symptomatic manifestations of systemic mastocytosis can either be triggered spontaneously or be precipitated by a variety of situations, stimuli, and exposures. Common gastrointestinal complaints include abdominal pain, diarrhea, nausea, vomiting, and gastrointestinal reflux disease. Substantial numbers of mast cells have been noted in patients who have been diagnosed with gastritis, ulcerative colitis, and Crohn disease. Irreversible, with symptoms that run the gamut from the merely annoying to the severely life-threatening, mastocytosis is a disease that prevents an individual from leading a normal life. As the prevalence of gastrointestinal symptomatology in those patients who have been diagnosed with mastocytosis is so significant, it is an important and relevant disease of which gastroenterology nurses should be cognizant.