Gastrointestinal stromal tumors (GISTs) occur most frequently in the stomach. Diagnosis of gastric GIST is not always clear before surgery. Flexible endoscopy may suggest the nature of the lesion (a bulky tumor with preserved mucosa); however, biopsy is rarely diagnostic. Therefore, diagnostic medication with safe drugs may provide a feasible way under such conditions after an informed consent is obtained. Based on the excellent efficacy of imatinib mesylate (IM) in the treatment of GIST, we successfully applied it in the diagnostic medication of two patients with clinically suspected gastric stromal tumors. In conclusion, the diagnostic medication with IM can be an alternative option for patients with suspected GIST that can not be confirmed pathologically.