Pancreatic and biliary carcinomas remain a challenge to clinicians and investigators, as diagnosis is rarely achieved while the tumor is still in a curative stage. Clinical symptoms and signs of these neoplasias are non-specific and heterogeneous. We review the clinical presentation of these tumors, with an emphasis on their pathophysiology and relationship with survival. Abdominal pain is the most common presenting complaint in pancreatic and biliary tract carcinomas, regardless of their size; although severe back pain usually indicates neural compromise, and is associated with a short survival. Jaundice may also be an early sign, in fact, pancreatic tumors that present as painless jaundice have been ascribed, a relatively more favorable prognosis. Weight loss is a common finding in most patients, being usually associated with malabsorption. These neoplasias may also present as diabetes, as an acute pancreatitis episode, with venous thrombosis or malignant thrombophlebitis, as a gastrointestinal hemorrhage, with mental disturbances, or skin manifestations.