Objective: To study the clinicopathologic features, pathogenesis, and differential diagnosis of inflammatory fibroid polyp (IFP) of the gastrointestinal tract., Methods: The clinical and pathologic findings of 37 IFPs in the gastrointestinal tract were retrospectively analyzed. Immunohistochemical study and KIT, PDGFRA molecular analysis were carried out and the literatures reviewed., Results: There were 9 males and 28 females. The median age was 57 (range 37 to 78) years. Twenty-two were in the antrum, nine in the ileum, three in the cardia, and one each in the gastric angle, corpora ventriculi and duodenum. The lesion ranged in size from 0.5 to 5.5 cm (mean 3 cm). Grossly, the majority appeared as a solitary non-encapsulated, submucosal, polypoid lesion. There was associated mucosal ulceration in three cases. Microscopically, the gastric lesions showed spindle-shaped cells arranged in an onion skin-like pattern around vessels and mucosal glands in a concentric formation. But the lesions in the ileum represented Vanek's tumor subtype devoid of concentric formations, with spindled to epithelioid cells dispersed in edematous stroma. Most of the lesions were in the mucosa and submucoma, but one small intestinal IFP infiltrated the muscularis propria. The inflammatory component of the lesions consisted predominantly of lymphocytes and eosinophils. Immunohistochemically, all cases displayed diffuse reactivity for vimentin and CD34; and 18 expressed PDGFRA. Analysis of KIT and PDGFRA mutations was performed in 18 cases. No KIT mutations were identified. However, four cases harbored activating mutations in PDGFRA exon 18 (D842V), five showed mutations in exon 12 (p.566-571delSPDGHEinsR). Follow-up in 30 cases showed no recurrence or metastasis., Conclusions: IFPs not only exhibit two morphologies, but also show mutations in the PDGFRA gene. IFP is a benign mesenchymal tumor rather than a reactive lesion.