Introduction Pancreatic adenocarcinoma (PA) remains one of the most aggressive malignant tumors of the digestive tract, with a five‐year survival rate of 5%. Although early detection offers the best chance to cure pancreatic adenocarcinoma, early stage disease presents little or no symptoms. The most commonly used marker for early detection of AP is serum CA19‐9, which has a sensitivity of 70% to 80%, however, with a specificity less than 50%. MiRNAs, endogenous small RNAs of approximately 17–25 nucleotides, present an altered expression in various cancers, suggesting its close relationship to disease processes, with the possibility of being a molecular biomarker for diagnosis and prognosis of cancer. Objectives To evaluate the effect of the combination of the association of anti‐apoptotic microRNAs: miR‐15a and miR‐16 and pro‐apoptotic microRNAs: miR‐21, miR‐221 and miR‐222 expression profile and the protein XIAP with serum CA19‐9 in diagnosis of diagnosis of pancreatic adenocarcinoma. Patients and Methods We studied 23 samples of PA and 20 as control samples: 13 of normal pancreatic tissue adjacent to the tumor (PPT), collected during pancreatic resections and 7 normal pancreas (NP) from deceased donors or patients who have undergone pancreatectomy affected by trauma. CA19‐9 was measured in serum and checked for expression of the miRNAs and XIAP in PA, PPT and NP through amplification by real‐time quantitative PCR (RT‐PCR). The usefulness of miRNAs and XIAP in the diagnosis of PA, alone or associated with CA19‐9, were analyzed by the construction of ROC curves. Results It was observed significant differences in the expression of miR‐21 in the comparison between the PA and NP groups (p<0.05). However, there was no significant difference in the expression of the protein XIAP between groups, as well as the expression of miR‐21 between groups NP and PPT. The combination of miR‐21 with CA19‐9 was more effective to discriminate the PA and NP (AUC‐ROC: 0.94; sensitivity: 78%, specificity: 99%) when compared with the assessments isolated. Conclusion The expression of miR‐21 was demonstrated to be effective in discriminating between PA and NP and the association between miR‐21 and CA19‐9 increased the sensitivity and accuracy in the diagnosis of PA in the sample studied. This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.