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Keisuke Taniuchi,1,2 Makiko Tsuboi,2 Masahiko Sakaguchi,3,4 Toshiji Saibara1,2 1Department of Endoscopic Diagnostics and Therapeutics, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan; 2Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan; 3Integrated Center for Advanced Medical Technologies, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan; 4Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa, Japan Background: The aim of this study was to investigate the use of podocalyxin (PODXL) and secretoglobin family 1D, member 2 (SCGB1D2) expressions in whole blood as diagnostic biomarkers to distinguish between patients with pancreatic cancer and control participants, in comparison with serum cancer antigen 19-9 (CA19-9), which is the current clinical standard. Patients and methods: Flow cytometric analysis was performed to determine the expressions of PODXL and SCGB1D2 on the surface of cultured pancreatic cancer cells. Immunoblotting was performed to determine whether PODXL and SCGB1D2 were detectable in the media of cultured pancreatic cancer cells. A discovery-stage clinical study was performed in a cohort of 23 patients with pancreatic cancer and 51 control individuals without pancreatic disease who had been treated in the Department of Gastroenterology and Hepatology at Kochi Medical School Hospital from April 2014 to January 2016. Serum PODXL and SCGB1D2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: PODXL and SCGB1D2 accumulated in the protrusions of cultured pancreatic cancer cells, and they were detectable both on the cell surface and in the cultured media from these cells. The discovery-stage clinical study showed that the area under the receiver-operating characteristic curve (AUC) was 0.96 (95% confidence interval [CI] 0.91–1.000) for PODXL, 0.80 (95% CI 0.67–0.94) for SCGB1D2, and 0.78 (95% CI 0.66–0.90) for CA19-9. The AUC for PODXL was thus significantly higher than that for CA19-9 (P = 0.006). The combination of SCGB1D2 with CA19-9 did not significantly increase the AUC (0.83; 95% CI 0.70–0.96) compared with the AUC for either SCGB1D2 or CA19-9 alone (P = 0.563). Conclusion: PODXL may be a novel, non-invasive diagnostic biomarker for the detection of pancreatic cancer. Keywords: podocalyxin-like protein, secretoglobin, pancreatic cancer, diagnostic marker