The diagnostic approach to pancreaticobiliary disease requires a multidisciplinary team in which the cytopathologist plays a crucial role. Fine-needle aspiration, obtained by endoscopic ultrasound, is the diagnostic test of choice for pancreatic lesions. Preoperative clinical management depends on many factors, many of which rely on accurate cytologic assessment. Pancreaticobiliary cytology is wrought with diagnostic pitfalls. Clinical history, imaging studies, cytology samples, and ancillary tests, including immunohistochemistry, biochemical analysis, and genetic sequencing, are integral to forming a complete diagnosis and guiding optimal patient management. This article reviews clinical aspects and the diagnostic work-up of commonly encountered diagnostic entities within the field of pancreatic cytology.