275 Background: Adenosquamous cell carcinoma (ASC) is an uncommon histologic variant of pancreatic cancer, representing only 1-4 % of all pancreatic neoplasms. Here we reported the extremely rare case of ASC derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreas with intensive pathological and molecular analysis. Methods: A 72-year-old diabetic male with five-year history of non-alcoholic chronic pancreatitis was admitted to our hospital with complaint of epigastric pain. The patient was diagnosed as pancreatic cancer associated with IPMN and pylorus preserving pancreaticoduodenectomy was performed in April 2012. The resected pancreas was fixed in 10% formaldehyde, and the whole specimen was sliced at a thickness of 5-mm for i) pathological analyses using hematoxylin-eosin (H-E) staining and immunostaining with specific antibodies against MUC-1, -2, -5AC, -6, p63 and CD5/6, and ii) deep sequencing of multiplex PCR amplicons of 50 cancer-associated genes utilizing Ion Torrent PGM platform. DNA was obtained from intraepithelial lesions of IPMN, invasive squamous cell carcinoma (SCC) and adenocarcinoma (AC) after enrichment for neoplastic cellularity, using manual microdissection. Results: Pathological findings showed IPMN extended from main pancreatic duct to branch ducts. The invasive tumor was predominantly consisted of poorly-differentiated SCC and small poorly-differentiated AC was also found in the edge of the SCC. All IPMN area analyzed shared combination of the mutations, KRASG12D and GNASR201C. The identical mutations in KRAS and GNAS as IPMNs were also found in SCC and AC. Conclusions: It generally difficult to fully discriminate IPMN-derived cancer (invasive IPMN) from concomitantly and independently developed de novo pancreatic ductal adenocarcinoma (PDA) originating from the “field defect”. In the current case, although SCC is a rare histotype of IPMNs, we considered that the invasive carcinoma was derived from IPMN based on their mutational profile.