Establishing the diagnosis of pancreatic cancer has improved significantly with the addition of EUS to the diagnostic armamentarium. The further introduction of FNA has allowed tissue conformation previously limited to percutaneous approach or at the time of surgical exploration. Consistently adequate tissue sampling to establish a diagnosis has been problematic with current technology. The significance of suspicious or atypical histology in the setting of pancreatic mass lesions is unclear. Aim: To determine the frequency and significance of suspicious or atypical histology in patients with pancreatic mass lesions. Methods: Over a 10-year-period, 286 patients were identified with pancreatic carcinoma confirmed by EUS-FNA, percutaneous CT-guided biopsy, surgical exploration or long-term follow-up. Of these, 191 patients underwent attempted EUS-FNA. During this period 26 patients with chronic pancreatitis with tumorous appearing parenchymal abnormalities underwent EUS-FNA. All patients had established benign disease by EUS-FNA and confirmed by surgery or long-term follow-up. EUS-FNA histopathology was reviewed and compared to final diagnosis. Pathology results included adenocarcinoma, benign/inflammatory, suspicious/atypical or insufficient. Patients with cystic neoplasm and neuroendocrine tumors were excluded from this review. Results: Overall accuracy of EUS-FNA for pancreatic carcinoma was 145/191 = 76%. The 46 (negative) cytology results included suspicious/atypical (n = 29, 15%), benign/inflammatory (n = 6, 3%) and insufficient (n = 11, 5.9%). Overall accuracy of EUS-FNA for chronic pancreatitis was 21/25 = 84%. The 4 incorrect cytology results included suspicious/atypical (n = 1, 4%) and insufficient (n = 3, 12%). The ability of suspicious/atypical EUS-FNA cytology in predicting pancreatic adenocarcinoma was highly specific (96%) with high positive predictive value (97%). The sensitivity and negative predictive value was comparatively lower (83% and 78% respectively). Conclusions: 1) EUS-FNA of pancreatic mass lesions is less than optimal. 2) The significance of suspicious and/or atypical histopathology in the setting of pancreatic mass lesions carries a high specificity and positive predictive value for pancreatic carcinoma. These results along with a positive cytology can be used collectively to increase the accuracy of EUS-FNA in pancreatic mass lesions. Tabled 1 EUS-FNA results Final diagnosis Pt. (n) ACA Suspicious/Atypical Benign Insufficient Pancreatic Cancer 191 145 29 6 11 Chronic Pancreatitis 26 0 1 21 3 ACA = Adenocarcinoma Open table in a new tab ACA = Adenocarcinoma