Objective: To investigate the histological and immunohistochemical features of 29 cases of epithelioid gastrointestinal stromal tumors (GIST), as well as the diagnosis and differential diagnosis, which is of great clinical significance for the clinical correct diagnosis, treatment and prognosis. Methods: A total of 321 cases of GIST were retrospectively analyzed from March, 2009 to August, 2016. Twenty-nine cases of epithelioid GIST were screened and re-examined. Results: Among 29 cases of epithelioid GIST, there were 15 cases of stomach, 2 cases of small intestine, 3 cases of mesentery, 4 cases of rectum, 3 cases of abdominal cavity, 1 case of retroperitoneum and 1 case of pelvic cavity. There were 25 cases of malignant GIST and 4 cases of benign. Tumor cells were rich, cytoplasmic was eosinophilic or transparent, the nuclear ratio of some tumor cells was high, nuclear size ranged and was polymorphic, more mitotic, accompanied by focal coagulation necrosis, interstitial cells were most associated with myxoid degeneration. The structures of tissue were organ-like, flake, nest and alveolar shape, etc. Immunohistochemical staining of CD34 and DOG-1 was positive in epithelioid GIST (positive rate 100%) and CD117 (positive rate 86%). Conclusion: Epithelioid GIST is widely distributed in many parts of the body, and it is easy to misdiagnose other epithelial-like tumors. Immunohistochemical staining of CD34, DOG-1 and CD117 is of great value in the diagnosis and differential diagnosis of epithelioid GIST, such as tumor mass, cell-rich, nuclear division, and mucinous stromal degeneration; the vast majority should consider the malignant GIST, so as to provide an important guiding significance for clinical correct diagnosis and treatment.