Pancreatic cysts are commonly found on cross-sectional imaging. The question arises in determining which lesions are premalignant or malignant and may require further testing, intervention, or follow-up. In pancreatic cysts without obvious malignancy on imaging, we approach them using the Four "S" Criteria. These are (1) symptoms that may be originating from the pancreatic cyst; (2) size of the cyst 2 cm or larger and/or main pancreatic duct greater than 5 mm; (3) survival of the patient, based on comorbidity index to determine surgical fitness; and then endoscopic ultrasound with fine needle aspiration (FNA) recommended to determine (4) solid component presence in the cyst, namely, nodule or thick walls, as well as to perform FNA to obtain cyst content. Current cyst fluid analysis options include use of cytology to determine presence of malignancy and carcinoembryonic antigen and fluid genetics to identify potentially premalignant lesions. The aims of this article are to explore current management guidelines for pancreatic cysts, present a comprehensive approach to pancreatic cysts, and explain the advantages and disadvantages of each option for evaluation of pancreatic cysts including endoscopic ultrasound with FNA with cyst fluid analysis using an evidence-based approach.