Previous studies have shown elevated serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) in patients with pancreatic cancer (PC). The aim of this study was to assess the diagnostic usefulness of pretreatment serum levels of IL-6 and CRP to differentiate between PC and chronic pancreatitis (CP) patients. Serum levels of CRP, IL-6, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA 19-9) were determined in 78 patients with PC before surgery, in 45 patients with CP, and in 70 healthy controls. Serum levels of all the proteins tested were significantly higher in cancer patients when compared with CP and healthy subjects, and increased in more advanced tumor stages. Concentrations of IL-6 were significantly higher in nonresectable tumors and in patients who died during the 2-year observation period. Area under receiver operating characteristic curve for IL-6 was higher than for other substances tested in the differentiation between PC and CP. Cox's univariate analysis revealed serum IL-6 as a significant prognostic factor of patients' survival. Our findings suggest higher diagnostic usefulness of serum IL-6 than CRP, CEA, and CA 19-9 in the diagnosis and prognosis of patients with PC and in the differentiation with CP.