Maspin, a member of the serpin family of serine protease inhibitors, has been shown to limit invasion and metastases in breast and prostate carcinomas. Maspin gene expression is up-regulated in pancreatic cancer, but not in normal pancreatic tissue. Maspin expression has been documented using immunohistochemical studies in pancreatic adenocarcinoma and high-grade intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic pancreatitis utilizing tissue microarray technology to determine the utility of maspin in differentiating these lesions. Immunohistochemistry was performed on tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24 cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or poorly differentiated using the WHO criteria. The primary antibody used was monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA). Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1+ to 3+ based on intensity. Cases were considered positive if one or more cores demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1+ to 2+) staining within occasional benign ductal epithelial cells in 29% of cases (7/24). Diffuse and intense (3+) staining was present in ducts with squamous metaplasia (3 cases). The majority of ducts showed no staining. Ductal adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally more intense staining than cases of chronic pancreatitis. Maspin may be helpful in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous metaplasia is ruled out.