Both autoimmune pancreatitis (AIP) and pancreatic cancer frequently present with obstructive jaundice. However, AIP is a rare disease and its diagnosis carries vastly different therapeutic and prognostic implications compared with that of pancreatic cancer. The clinical challenge is to distinguish AIP from pancreatic cancer, because the price of misdiagnosis can be heavy. Recently, two strategies for differentiating AIP from pancreatic cancer were published, one from Japan and the other from the United States. The Japanese strategy relies on cross-sectional imaging, endoscopic retrograde pancreatogram, and serum IgG4. The American strategy uses imaging (CT scan), serology (serum IgG4), and evidence of other organ involvement (on CT scan) as the first tier of tests. If the differentiation cannot be made by these methods, a core biopsy of the pancreas, steroid trial, or surgical resection is recommended. The two strategies reflect differences in clinical practice and local preferences in the use of certain diagnostic tests. However, both strategies require thorough familiarity with the diseases and the tests being used.