Background: EUS-guided FNA is a well-recognized technique for sampling the pancreas, peri-intestinal lymph nodes, and mass lesions. The role of EUS-guided FNA in the diagnosis of peritoneal carcinomatosis has not been well studied. Objective: We aimed to determine the feasibility and success in sampling lesions in the peritoneum suspicious for carcinomatosis without a primary source. Design: An observational study. Setting: A tertiary referral center. Patients: Consecutive patients who underwent EUS-guided FNA of peritoneal deposits. Results: During a span of 3 years, 4 patients underwent transgastric or transduodenal EUS-guided FNA of peritoneal lesions with a curvilinear echoendoscope. All of these lesions were imaged by abdominal CT scan. The EUS findings of the nodules appeared round, relatively hypoechoic to the surrounding tissue, but hyperechoic when compared with the surrounding low-volume ascites where the lesions floated. Four passes were performed per case, and the diagnosis was achieved on a median of 2 passes (range 1-4). All patients received intravenous antibiotics during the procedure. Two patients had metastatic adenocarcinoma, 1 patient had lymphoma, and 1 patient had metastatic breast carcinoma. Diagnostic laparoscopy/laparotomy was avoided in all patients. No complications, particularly peritonitis, were encountered. Limitations: Observational study with a small sample size. Conclusions: Transgastric or transduodenal EUS-guided FNA for peritoneal carcinomatosis is feasible and safe. In the setting of an unknown primary cancer, EUS-guided FNA facilitates acquisition of tissues for treatment allocation, thus avoiding the need for laparoscopy or laparotomy. © 2009 American Society for Gastrointestinal Endoscopy.