Twenty-one consecutive cases of gastrointestinal spindle cell stromal tumors (SCSTs) were studied histologically and immunohistochemically. They consisted of 18 smooth muscle tumors, 2 neurilemmomas (schwannomas), and 1 unclassified malignant tumor designated as stromal sarcoma. Slender, spindle and wavy nuclei with palisading associated with peripheral tumor aggregation of lymphocytes are the pathological hallmarks of neurilemmoma. With peroxidase-antiperoxidase method, antibodies to Glial Fibrillary Acidic Protein (GFAP), Leu-7, S-100, desmin and HHF35 were applied. Antibodies to Leu-7 and GFAP could only be demonstrated in neurilemmomas (2 cases). Antibody to S-100 was observed strongly in 2 neurilemmomas and 1 stromal sarcoma, and focally in a leiomyoma, while the other SCSTs were negative. One neurilemmoma disclosed focal positivity of desmin. Six of 10 leiomyomas revealed varied degrees of positive staining of desmin and HHF35. One epithelioid leiomyoma, two leiomyosarcomas and five smooth muscle tumors of undetermined malignant potential (STUMP) disclosed no immunoreactivity. The study suggests that panel of immunostaining should be applied. Coexpression of GFAP, Leu-7 and S-100 as well as negative staining of HHF35 is characteristic of neurilemmoma. On the contrary, coexpression of desmin and HHF35 while negative for GFAP, S-100 and Leu-7 are suggestive of smooth muscle tumor. In poorly differentiated SCST, histological features and immunostains are always disappointing. Diagnosis of those tumors as stromal tumor is more appropriate or electron microscopic observation should be included for accurate classification.