Discrimination between the well differentiated pancreatic carcinoma and the chronic fibrotizing pancreatitis is one of the most difficult diagnostic problems in the field of pancreatology, and it is also a challenge for the pathologist. The author outlines those objective facts that might lead to diagnostic errors. The two diseases may coexist; on the one hand, malignant tumor can be developed as a complication of a long-standing chronic pancreatitis, while on the other hand, pancreatic carcinoma is frequently accompanied by chronic inflammation. The majority of adenocarcinomas induce a striking desmoplastic stromal reaction, but the chronic pancreatitis is also characterized by a vigorous fibroblast proliferation leading to the possibility of macroscopical misdiagnosis. Microscopically, the pancreatitis can be mistaken for carcinoma, because the actively growing connective tissue irregularly separates the ducts and in addition, the continuous regenerative activity may lead to regressive atypia. For that reason, cytopathologist must evaluate several criteria together, because the nuclear alterations by themselves can be misleading. Although there are some promising new differential diagnostic techniques (apomucins, CAM 17.1, telomerase activity, loss of chromosome Y), so far the most reliable method has been the meticulous evaluation of the cellular and histological findings by the well trained pathologist. To date, molecular pathological methods have shown no advantage in the differential diagnosis.