Since surgical resection of localized tumors improves overall survival, early detection of pancreatic cancer would have substantial health benefits . For early detection, high specificity is especially important. In this study, we devised a NOIR-SS-based assay for a panel of genes related to pancreatic cancer. In the first step, variants, including those present in healthy individuals, are identified. Therefore, we developed a bioinformatic filter to remove variants that are unlikely to be somatic mutations in cancer tissues. The results showed that the filter completely removed such inappropriate variants. The performance of the assay and filter system was validated using an independent cohort of patients with intraductal papillary mucinous neoplasm (IPMN) and pancreatic cancer. Sequencing based on molecular barcodes along with the filter we developed is likely to eliminate most variants not specific to cancer cells, while maintaining sensitivity comparable to that of conventional digital PCR/deep sequencing.