Patients with chronic pancreatitis (CP) are at risk of developing pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, there are no suitable non-invasive biomarkers for differentiation between CP and PDAC; however, potential molecular candidates include circulating miRNAs due to ease of extraction, their stability and tissue specificity. Therefore, the aim of the present study was to identify potential serum marker(s) that may be used for differentiating between CP and PDAC. In total, 77 patients were enrolled in the present study; 34 patients with CP, 26 patients with PDAC and a control group of 17 healthy individuals. Expression of miR-10b-5p, miR-106b-5p, miR-210-3p and miR-216a-5p in serum was determined by reverse transcription-quantitative PCR. Serum miRNA expression levels in patients with CP, PDAC and in the control group were compared. Routine biochemical blood parameters were determined and correlation analysis of these parameters with miRNA expression was performed. Expression of miR-210-3p was increased in the sera of patients with PDAC compared with the CP patients (P=0.015) and with the control group (P<0.001). MiR-106b-5p (P=0.056) and miR-10b-5p (P=0.080) were not significantly upregulated in patients with PDAC compared with those with CP. Analysis of miRNA expression in relation to laboratory blood parameters showed positive correlations between miR-210-3p with alkaline phosphatase (r=0.605; P=0.022) and with γ-glutamyltranspeptidase (r=0.529; P=0.029) in PDAC. The novel finding of the present study was that miR-10b-5p was positively correlated with C-reactive protein (r=0.429; P=0.047) in patients with PDAC and with carbohydrate antigen 19-9 (r=0.483; P=0.005) in CP. Based on the preliminary data obtained in the present study, it was concluded that miR-210-3p may be used as a non-invasive biomarker that can be used to distinguish between patients with PDAC and CP.