Conclusions: Activation of the immune system in pancreatic cancer is demonstrated by increased serum levels of neopterin, soluble Interleukin 2 receptor (sIL-2R), and Interleukin 6 (IL-6). Determination of these parameters does not provide benefit in the diagnosis of pancreatic cancer. Background: The aim of the study was to define the diagnostic value of serum neopterin, an in vivo marker of macrophage activity, in pancreatic cancer. Methods: Thirty-four patients with pancreatic cancer were studied. According to the UICC TNM classification 6 were in stage I, 9 in stage II, 6 in stage III, and 13 in stage IV. Twenty-four patients with chronic pancreatitis, 72 healthy blood donors, and 20 patients with jaundice resulting from gallstones were used as control groups. Neopterin, tumor necrosis factor (TNF), sIL-2R, and IL-6 were measured in serum in the different groups; Ca 19-9 was also measured in cancer and pancreatitis. Results: Serum levels of neopterin, sIL-2R, and IL-6 were higher in cancer than in pancreatitis and healthy donors, and in pancreatitis higher than in donors. Serum TNF was similar in the three groups. Serum levels of neopterin, TNF, sIL-2R, and IL-6 were not related to the tumor stage or to Ca 19-9 levels. A positive correlation was found between sIL-2R and neopterin levels. Neopterin levels in obstructive jaundice were similar to those of pancreatitis. Ca 19-9 at the recommended cutoff of 37 U/mL showed the best sensitivity and specificity (88.2 and 87.5%, respectively). At the selected cutoff neopterin, TNF, sIL-2R, and IL-6 showed low sensitivity and specificity in differentiating cancer from pancreatitis.