Current National Comprehensive Cancer Network (NCCN) guidelines recommend CGP for patients with locally advanced/metastatic PDAC in order to identify actionable mutations for specific anticancer therapy. The majority of PDACs are diagnosed by EUS-FNA/B; however, corresponding tissue specimens are frequently inadequate for CGP. We hypothesized that a dedicated pass during the diagnostic EUS-FNA/B procedure submitted in nucleic acid stabilization buffer could improve the yield of neoplastic DNA and RNA for CGP and, therefore, a prospective, observational study was performed. Within a 13 month period, 98 prospective patients had PDAC diagnosed via an EUS-FNA/B of a pancreatic mass. At the time of the diagnostic procedure, a separate, dedicated pass was entirely submitted in nucleic acid stabilization buffer for CGP upon request. As clinically indicated, CGP was performed on the stored pass using an amplicon-based sequencing panel of 161 cancer-associated genes and 760 known fusion genes. Patient demographics, imaging findings, cytology diagnosis, cell block adequacy and CGP results were evaluated. The patient cohort consisted of slight male predominance (n=54, 55%), and the majority of PDACs were located in the pancreatic head (n=46, 47%) and body (n=24, 25%). CGP was requested for 67 (68%) patients; however, the corresponding cell blocks were insufficient for 29 of 67 (43%) cases. Among these 29 patients, tumor DNA and RNA were isolated from the dedicated pass with yields ranging between 25 to 310 ng (mean, 138 ng) and 49 to 1411 ng (mean, 477 ng), respectively. Cell blocks among the remaining 38 patients with sufficient neoplastic epithelium had comparable DNA and RNA yields that ranged between 44 to 632 ng (mean, 221 ng; p=0.197) and 18 to 1097 ng (mean, 358 ng; p=0.576). Using the dedicated pass, CGP successfully identified pathologic genomic alterations in all 29 cases. In contrast, 2 of 38 (5%) cases using cell block material only, failed due to poor DNA and RNA quality. Finally, in one patient diagnosed as PDAC by rapid on-site evaluation, the final diagnosis was revised to "suspicious for carcinoma” and the corresponding cell block was insufficient for ancillary studies. CGP of the patient’s dedicated pass revealed multiple genomic alterations that were consistent with PDAC, enabling the patient to receive neoadjuvant therapy and avoid a repeat procedure. Our results support CGP is increasingly used by oncologists to identify actionable targets for therapy. We propose that a dedicated pass stored in nucleic acid stabilization buffer yields sufficient DNA/RNA for CGP, can assist in confirming the diagnosis and potentially alter treatment course and prognosis.