Pancreatic cancer is one of the most malignant cancer types and has a poor prognosis. It is often diagnosed at an advanced stage because of the absence of typical symptoms. Therefore, it is necessary to establish a screening method for the early detection of pancreatic cancer in high-risk individuals. This is a prospective validation study conducted in a cohort of 1033 Japanese individuals (male, n = 467, age = 63.3 ± 11.5 years; female, n = 566, age = 64.2 ± 10.6 years) to evaluate the use of salivary polyamines for screening pancreatic diseases and cancers. Patients with pancreatic cancer were not included; however, other pancreatic diseases were treated as positive cases for accuracy verification. Of the 135 individuals with elevated salivary polyamine markers, 66 had pancreatic diseases, such as chronic pancreatitis and pancreatic cysts, and 1 had gallbladder cancer. These results suggest that the salivary polyamine panel is a useful noninvasive pancreatic disease screening tool.