Background: SIGIMs occur anywhere in the GI tract and may be benign or malignant. Forceps biopsy at EGD is low yield and diagnosis based solely on EUS-appearance may be misleading. Experience with EUS-FNA of these lesions is limited to small series and specific diagnoses. Objectives: To assess a)the diagnostic yield of EUS-FNA in SIGIMs of different echogenicities and b)the ability of EUS-FNA to obtain sufficient tissue for immunohistochemisty (IHC) when relevant. Methods: EUS-FNA was attempted in all pts undergoing EUS evaluation of SIGIMs. FNA was performed using 22, 19 or 25 ga needles depending upon available technology. Experienced cytopathologists performed on-site interpretations to assess adequacy. Extrinsic compressions, strictures and thickfold gastropathies are not included. Results: 101 pts with 105 lesions had FNA between 6/1998 and 12/2003. Repeat FNA was performed in 5 lesions (total 110 FNAs: 57 stomach, 40 esoph, 10 duod, 3 colon). There were 12 intramural cysts (6 anechoic, 6 hypoechoic): none yielded diagnostic cytology (all yielded fluid, 7/12 were grossly mucoid). 93 solid lesions were aspirated and results shown in the table below. Repeat FNA was diagnostic in 2 of 4 hypoechoic masses, leading to overall yield of 83% for hypoechoic lesions. EUS-FNA identified 9 carcinomas (7 metastatic, 2 primary esophageal); 59 mesenchymal neoplasms (37 GIST, 12 leiomyomas, 1 glomus tumor, 2 peripheral nerve sheath tumors, 1 granular cell tumor, 1 lipoma, 5 unspecified spindle cell tumors) and 1 pseudocyst. When IHC was needed based on initial smear results, adequate paraffin-embedded material was present in 79%. Among 24 non-dx cases, 4 had characteristic EUS features for lipoma, 4 had EGD/EUS features suggesting pancreatic rest, 2 were later proven GIST, 1 proven granular cell tumor, 1 proven Brunner's adenoma and 12 remain unknown. Conclusions: The yield of EUS-FNA for solid, hypoechoic intramural tumors was excellent. Sufficient material for IHC was often obtained when needed. The yield of FNA for suspected lipomas or pancreatic rests was very low. Diagnostic cytology was not obtained in intramural cysts (suspected duplication cysts) but FNA established their cystic nature. Carcinoma was diagnosed in 9% of solid lesions.