Introduction: Chemokine receptors may have a critical role in the metastasis and progression of invasive malignancies. There is little data, however, regarding chemokine receptors and premalignant lesions. Our objective was to determine the potential role of chemokine receptors in pancreatic intraepithelial neoplasia (PanIN), the precursor lesion to invasive pancreatic duct cancer. Methods: The PanIN cell line, established from the PDX-1-Cre;LSL-K-RASG12D mouse, was assessed by cDNA microarray analysis (Affymetrix Mouse Genome 430 2.0 array) for chemokine receptor expression. The invasive pancreatic duct cancer (5143PDA) and liver metastasis (5143LM) cell lines from the PDX-1-Cre;LSL-K-RASG12D/p53R172H mouse and human pancreatic cancer cell line PANC-1 were obtained to further investigate microarray results. Paraffin-embedded murine PanIN tissues and human PanIN and invasive pancreatic cancer specimens were obtained to verify chemokine receptor expression. Results: Microarray analysis of cultured PanIN cells revealed CCR9 to have the highest gene expression of any chemokine receptor. CCR9 protein expression was verified by Western blot assay in PanIN, 5143PDA, and 5143LM cells. The level of CCR9 protein expression was observed to increase from PanIN to invasive cancer to liver metastasis. Of note the human pancreatic cancer cells PANC-1 exhibited the highest level of CCR9 expression. Immunohistochemistry of paraffin-embedded murine and human PanIN lesions verified CCR9 protein expression showing heterogeneous and moderately intense immunoreactivity for CCR9 within the cytoplasm and cell surface of PanIN lesions. More intense, homogeneous immunoreactivity for CCR9 was observed in human pancreatic cancer lesions. Conclusions: This is the first report of chemokine receptor CCR9 expression in murine and human PanIN tissues. Our results suggest a potential upregulation of CCR9 expression during PanIN progression. Further work may prove this chemokine receptor to be a novel target for PanIN and its progression to invasive cancer.