Introduction: Accurate differential diagnosis between chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) is still problematic. Difficulties arise from the fact that the imaging techniques, clinical symptoms, and laboratory parameters of these 2 diseases are similar. Therefore, non-invasive markers to clearly distinguish between these 2 disorders are urgently needed, and microRNAs (miRNAs) seem to be the most promising biomarkers, because of their tissue specificity, stability in different biofluids, and easy detection.Aim of the research: To evaluate the usefulness of the measurement of selected miRNAs and basic clinical parameters as a test for differentiating PDAC from CP.Material and methods: The expression of miR-21-5p, miR-23a-3p, miR-155-5p, miR-191-5p, miR-196a-5p, miR-205-5p, and miR-1290 was assessed in 74 serum samples (PDAC n = 26, CP n = 34, and the control group n = 14) by reverse transcription -quantitative PCR (RT-qPCR). Correlations between the levels of miRNAs and pancreatic lipase, amylase, alanine aminotrans-ferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), g-glutamyltranspeptidase (GGTP), haemoglobin (Hb), bilirubin, C-reactive protein (CRP), and CA19-9 were analysed in 3 groups.Results: We found that 2 combinations of miRNAs with blood parameters had diagnostic value. In PDAC the expression of miR-1290 positively correlated with GGTP activity (p = 0.029, rs = 0.487) and CA 19-9 level (p = 0.026, rs = 0.464), while in CP patients miR-191-5p expression was negatively correlated with amylase (p = 0.018, rs = -0.408) and CRP (p = 0.023, rs = -0.394). No statistically significant correlations were noticed between miRNAs and clinical parameters in the control group.Conclusions: The combination of miR-191-5p with CRP and amylase characterized CP, while miR-1290 with GGTP and CA 19-9 was specific for PDAC. These non-invasive tools can help to differentiate PDAC from CP.