CXC chemokines influence angiogenesis, growth, and metastatic potential of pancreatic cancer. Therefore, the expression and potential function of CXCL14, a recently described CXC chemokine, was evaluated. CXCL14 is upregulated in pancreatic cancer tissues compared to chronic pancreatitis and normal pancreas. Immunolocalization revealed a distinct expression of CXCL14 in tubular complexes in chronic pancreatitis and in particular at the invasive front of pancreatic cancer tissues. Stimulation of pancreatic cancer cells with CXCL14 showed no effects on cell viability and on chemosensitivity. However, CXCL14 clearly increased invasiveness of pancreatic cancer cells without affecting MMP-2 and VEGF secretion, whereas CXCL14 influenced NFkB p65 levels. In conclusion, CXCL14 might play a pivotal role in the pathobiology of pancreatic cancer, probably by regulating cancer invasion.