IκB kinase (IKKɛ) is a serine/threonine protein kinase that belongs to the IKK kinase family. Recent studies have shown that IKKɛ functions as a breast and ovarian cancer oncogene. We demonstrated frequent overexpression of IKKɛ in pancreatic ductal adenocarcinoma (PDA). We immunohistochemically evaluated 78 PDAs using the avidin-biotin-peroxidase method and the anti-IKKɛ rabbit polyclonal antibody. Elevated IKKɛ reactivity (immunohistochemical score, 4–9) was observed in 64% of PDAs (50/78), but in 0.0% of nonneoplastic pancreatic ductal epithelium (0/113; P < .001). Kaplan-Meier analysis of overall survival revealed that patients with high IKKɛ-immunohistochemical scores (4–9) had significantly shorter survival than did patients with low IKKɛ immunohistochemical scores (0–3; P = .023; log-rank test) independent of tumor stage or grade. These data indicate that deregulation of IKKɛ is a common event in PDA and might have an important role in the pathogenesis of this deadly disease. In addition, IKKɛ could serve as a prognostic marker and potential therapeutic target for PDA intervention.