Introduction: Abdominal pain and diarrhea are among the most common reasons patients are referred to gastroenterologists. In most cases, a cause can be identified during initial work-up following general guidelines; however, there are few cases where the diagnosis may not be straight forward. Mastocytic enterocolitis is a rare, recently defined disorder characterized by an increased number of gut mucosal mast cells (>20 per high power field) that are revealed by immunohistochemical demonstration of mast cell tryptase in patients with chronic diarrhea. This disorder can be easily missed if immunohistochemical staining for mast cells is not done. As these patients typically respond well to histamine receptor antagonists, antileukotrines, and inhibitor of mast cell degradation, it is important consider mastocystic enterocolytis in the differential diagnosis when evaluating patients with unexplained diarrhea. Methods: A clinical Vignette is presented. Results: We present a case of a 53-year-old male with 9-12 months’ history of abdominal pain and diarrhea. He reported 5-6 loose bowel movements per day, which were often explosive. He denied flushing, pruritus, rash, blood in stool, black stools, and mucus in stools. He reported a 15-pound weight loss over the past year. Initial labs revealed normal CBC, CMP, amylase, TSH. Given remote alcohol abuse and slightly elevated lipase (75U/L), he underwent an endoscopic ultrasound of the pancreas, which was also normal. The patient also underwent upper endoscopy, which showed diffuse erythema in the gastric antrum and body, with biopsies revealing minimal chronic inflammation. Colonoscopy showed normalappearing terminal ileum and colonic mucosa. However, immunohistochemical staining for tryptase on the biopsy specimens from the colon revealed 36 mast cells per high-power field. The patient started montekulast 10 mg daily with complete resolution of his symptoms after a few days. He remained symptom free on follow-up several months later. Conclusion: Mastocytic enterocolitis should be considered in patients with chronic diarrhea who’s initial work-up have been unrevealing.