Background: EUS-guided FNA is a sensitive method for the diagnosis of malignancy. However, EUS-FNA is often laborious and usually requires the presence of a cytopathologist or cytotechnician. The development of an EUS-guided Trucut biopsy (EUS-TCB) needle may simplify the procedure and expand the application of EUS-directed procurement of biopsy specimens. The aim of this study was to determine the feasibility of using the EUS-TCB for the diagnosis of intraintestinal and extraintestinal lesions and compare the results with this needle with those of EUS-FNA. Methods: The EUS-TCB and EUS-FNA were used to evaluate patients with known or suspected intraintestinal or extraintestinal mass lesions and/or lymphadenopathy. Patient records were retrospectively reviewed to determine the accuracy and safety of both techniques. Results: Nineteen patients had tissue samples obtained with both the EUS-TCB and EUS-FNA from 20 sites (2 sites in 1 patient) between December 2001 and March 2002. Accuracy was higher with EUS-TCB than EUS-FNA, although the difference was not significant (85% vs. 60%), despite performing fewer passes with the former (mean [SD] 2.0 [0.7], range 1-4; vs. mean 3.3 [1.5], range 1-10; p < 0.05). No complications were identified. Conclusions: This preliminary study suggests EUS-TCB can safely be used to obtain biopsy specimens of intraintestinal and extraintestinal mass lesions and lymphadenopathy. Its use may reduce the number of needle passes compared with EUS-FNA. This may reduce costs by shortening the procedure, diminishing the need for an onsite cytopathologist or technician, and lowering the frequency of nondiagnostic procedures. Prospective studies are needed to verify these findings.