Long standing chronic pancreatitis is a risk factor for developing pancreatic cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an increased risk of developing pancreatitis. The aim of this study was to determine if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of developing pancreatic cancer through the development of chronic pancreatitis. DNA from patients with histologically-confirmed surgically-treated chronic pancreatitis, familial and sporadic pancreatic adenocarcinoma and controls were analyzed for the N34S polymorphism of SPINK1 and the two commonest polymorphisms of the CFTR gene, the DF508 mutation and the 5T polymorphism. These polymorphisms were determined using restriction fragment length polymorphism, PCR and cycle sequencing methods. The SPINK1 N34S polymorphism was detected in 5 of 172 (2.9%) patients with chronic pancreatitis, in 4 of 200 (2.0%) patients with sporadic pancreatic adenocarcinoma, in 0 of 36 (0%) of patients with familial pancreatic cancer and in 3 of 177 (1.7%) controls of chronic cholecystitis. The CFTR 5T polymorphism was identified in 31 of 334 (9.3%) patients of sporadic pancreatic cancer, in 5 of 43 (11.6%) patients with familial pancreatic cancer and in 10 of 112 (8.9%) controls with colorectal cancer. The CFTR DF508 mutation was recognized in 6 of the 240 (2.5%) patients with pancreatic adenocarcinoma, a prevalence similar to that of control populations. We conclude that the N34S polymorphism of SPINK1 and the 5T and DF508 CFTR polymorphisms do not predispose to the development of pancreatic adenocarcinoma. Furthermore, the N34S polymorphism is rarely found in patients with severe idiopathic chronic pancreatitis.