BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed late, with an extremely poor prognosis. Treatment options like surgery, radiation, and chemotherapy are rarely curative. Tumor progression from primary to metastatic PDAC remains poorly understood at the molecular level. METHODS: In the current study, we analyzed the molecular profiles of metastatic PDAC obtained via the Oncomine Comprehensive Assay in comparison to primary PDAC. RESULTS: The current study cohort consisted of 115 metastatic PDAC cases, of which 71 (62%) cases succeeded in molecular testing while the remaining 44 (38%) cases contained insufficient tumor cells. Molecular profiling of 71 cases revealed a total of 239 molecular alterations, 3.4 alterations per case on average, predominantly in the form of gene mutations. The most common gene mutations included CONCLUSIONS: These findings suggest that metastatic PDAC possesses unique genetic characteristics, offering potential therapeutic targets in advanced-stage pancreatic cancer.