OBJECTIVE. The objective of our study was to determine the usefulness of sonographic guidance for biopsy of mesenteric masses. MATERIALS AND METHODS. Twenty-five sonographically guided percutaneous biopsies of mesenteric masses were performed in 23 patients. Biopsies were performed with an 18-, 20-, or 22-gauge self-aspirating needle or core biopsy device. Final pathology results and patient medical records were reviewed for biopsy accuracy and complications. A biopsy was considered successful if a specific benign or malignant diagnosis was rendered by the pathologist or if surgical-pathologic confirmation was obtained. RESULTS. Open surgical biopsy was performed after sonographically guided biopsy in 13 patients and led to 12 concordant diagnoses (nine true-positives and three true-negatives) and one discordant diagnosis (false-negative). Specific pathologic diagnosis was rendered for the 10 percutaneous biopsies that were not confirmed by surgical biopsy: five biopsies matched known primary malignancies, consistent with metastases; four biopsies revealed primary tumors, and one biopsy revealed chronic inflammation (nine true-positives and one true-negative). Two biopsies were nondiagnostic because of insufficient material (n = 1) and necrotic tumor (n = 1). In the biopsies with diagnostic tissue specimens, sonographically guided biopsy achieved a sensitivity of 95% (18/19) and specificity of 100% (4/4) for allowing neoplastic tissue to be distinguished from nonneoplastic tissue. Complications included a mesenteric hematoma and abdominal wall cellulitis. CONCLUSION. Percutaneous biopsy of mesenteric masses is a useful and safe procedure.