Background: General knowledge about autoimmune pancreatitis (AIP) has evolved rapidly during the last decades. Numerous diagnostic criteria have been proposed since the first Japanese criteria in 2002. Many criteria emphasize the challenge of differentiation between AIP and pancreatic cancer (PC). Methods: With the intension to differentiate AIP and PC before surgery, we conducted a search in PubMed. Results: AIP and PC have similar clinical picture and can t be differentiated based on the clinic. AIP is often IgG4 positive and PC can be CA19-9 positive. Serology is helpful, but not conclusive. Diffuse enlargement of the pancreas on CT/MRI is typical for AIP, but it may be impossible to discriminate focal AIP from PC. Diagnosis can be acquired by histology. While EUS-FNA biopsy often is successful in PC, EUS-FNA often contains too little tissue architecture for AIP diagnosis. Type 1 AIP can be recognised by typical affection of other organs. The diagnostic use of response to steroids remains controversial, but might be helpful as a last resort. Discussion: We propose a diagnostic strategy with initial CT. Focal enlargement should undergo cancer work-up. Both diffuse enlargement and focal enlargement with negative cancer work-up should be tested for serology, other organ affection, biopsy or/and steroid responsiveness. Negative supplementary tests should lead to reevaluation of malignancy. Conclusion: In most cases of AIP it will be possible to differentiate AIP from PC, but focal AIP with negative serology and type 2 AIP remains a diagnostic challenge.