Purpose: Predictors of malignancy in pancreatic cystic neoplasms include symptoms, pancreatic main duct dilation, mural nodularity, and cyst size. Cysts ≥3 cm are believed to correlate with malignancy, and this impacts current management strategies and practice guidelines. Aim: To identify clinical, endosonographic, laboratory, and pathologic factors that are associated with pancreatic cyst size ≥3 cm or <3 cm. Methods: This is a retrospective study performed at a Pancreas Referral Center. All subjects underwent an endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic cystic neoplasms from 6/2006 to 5/2011. Data collected include: demographics (age, gender, race), clinical features (symptoms), EUS findings (size, septations, nodularity), laboratory data (cyst fluid CEA, k-ras, LOH, cytology), and surgical pathology (malignancy defined as high-grade dysplasia, carcinoma in situ, and invasive carcinoma). Univariate and multivariate logistic regression analyses were performed on these variables to measure association and identify predictive variables (SPSS version 16.0). Results: There were 239 patients with pancreatic cystic lesions evaluated with EUS-FNA of which 68/239 (28.5%) were ≥3 cm. Mean age was 63.7 yr with 66% (157/ 239) female and median follow-up 10 months. Evaluation of Pancreas Cyst Size: presence of symptoms (p = 0.001) and absence of k-ras mutation (p = 0.043) were associated with cysts ≥3 cm while malignant pathology was not related to cyst size (p = 0.315). For cysts ≥3 cm, 1.5% (1/68) were malignant while 4.7% (8/171) were in cysts <3 cm. Only symptoms (p = 0.008) remained significantly associated with cysts ≥3 cm in multivariate logistic regression analysis when controlling for age, gender, and race. Conclusion: Pancreatic cystic neoplasms ≥3 cm are not associated with malignancy and k-ras mutation compared to cysts <3 cm. Larger pancreatic cysts are more likely to be symptomatic. Improved biomarkers are necessary to guide management of pancreatic cystic neoplasms regardless of cyst size.