Secreted Protein Acid and Rich in Cysteine (SPARC) is an extracellular glycoprotein secreted by fibroblasts and osteoblasts in normal tissues. SPARC overexpression occurs in multiple tumors including pancreatic ductal adenocarcinoma (PDAC) and may predict favorable response to nab-paclitaxel. The prognostic significance of SPARC expression in PDAC is unclear – some reports indicate SPARC overexpression associates with poor outcomes and others find no correlation. Considering neoadjuvant therapy enhances the stromal fibrosis of PDAC and taking into account that SPARC is a component of PDAC stromal fibrosis, we hypothesized that SPARC expression would be greater in neoadjuvant-treated versus treatment-naive PDAC. Quantitative immunohistochemistry was used to measure SPARC expression in resected PDAC in 74 cases of neoadjuvant treated PDAC and 95 cases of treatment-naïve PDAC. SPARC expression was increased 54% in neoadjuvant treated PDAC compared to treatment-naïve PDAC. These data indicate that increased SPARC expression correlates with neoadjuvant therapy in PDAC.