Background: To understand the role of islet amyloid polypeptide (IAPP) in type 2 diabetes and pancreatic cancer (PC), we investigated the patterns of its expression and its ratio to insulin, glucagon, somatostatin and pancreatic polypeptide cells by morphometry in tissues from these two diseases in comparison to the normal pancreas. Materials and Methods: Pancreatic tissues from 11 donors (five without pancreatic disease and six with type 2 diabetes) and 11 surgical specimens from PC patients obtained from the cancer area (zone A) and the adjacent tumor-free area (zone B) were examined immunohistochemically. The size of islets, the number on beta-, alpha-, delta-pp- and IAPP-expressing cells and their ratios in the islets of these tissues were determined. Results: In the normal pancreas, only 50% of the beta-cells while alpha- and delta-cells co-expressed IAPP only sporadically. In tissues from diabetics as well as in zone A, the number of the beta-cells and the IAPP-expressing cells was reduced significantly, while the number of alpha- and beta-cells was increased. In zone B, however, significantly more alpha-cell and IAPP-expressing cells and a significantly lower number of alpha-cells were found compared to those in zone A. Significant differences were also found between the specimens from type 2 diabetics and pancreatic cancer relative to the ratios of IAPP/beta-cell, IAPP/alpha-cells and beta-cell/delta-cells. Conclusion: The morphometric data show a decrease rather than an increase in the number of IAPP-expressing cells in PC. Differences in abnormalities in type-2 diabetics and in zone B of PC tissue strongly argue against the role of type 2 diabetes in PC. Rather, the development of diabetes in subjects prone to pancreatic cancer could be a red flag for malignancy.