By means of the differential display method, we isolated a novel human gene that is expressed specifically in pancreas. The cDNA, designated "pancpin," contained an open reading frame of 1,215 nucleotides encoding a 405 amino acid protein, showing a high degree of similarity to serine protease inhibitors belonging to the serpin superfamily. To investigate its possible role in pancreatic carcinogenesis, we looked for genetic alterations of this gene in pancreatic cancer cell lines and primary pancreatic cancer tissues. Expression of pancpin was barely detectable in any of the four pancreatic cancer cell lines examined, and very weak also in 10 of 13 pancreatic cancer tissues. A somatic missense mutation at codon 221 was found in two of 16 primary pancreatic cancers. These findings indicate that down-regulation of pancpin expression may play a significant role in development or progression of pancreatic cancer.