Background and aims:To evaluate the advantages of endoscopic ultrasound (EUS) in the assessment of detailed structures of pancreatic cystic lesions (PCLs) compared to computed tomography (CT) and magnetic resonance imaging (MRI). Methods: This prospective cohort study was conducted in Tropical medicine department, Zagazig university hospitals and in Internal medicine department at Kasr Al Aini Hospitals, Cairo University, in the period between March 2018 and March 2020. The study included 72 patients with PCLs, 29 were males and 43 were females, there ages ranged from 25 to 75 years. All cases were subjected to the following careful history taking, thorough clinical examination, laboratory investigations (CBC, LFTs, KFTs, Coagulation profile, serum amylase, serum CA 19.9), imaging (CT and/or MRI abdomen), endoscopic ultrasound examination and EUS-FNA biopsies using the 22G or 19G needle. Results:Validity of abdominal CT/MRI imaging, EUS, cytopathology and EUS with cytopathology was calculated using diagnostic performance depend on sample 2x2 contingency tables generation. Sensitivity, specificity, PPV, NPV and accuracy and their corresponding 95% CI were calculated. P-value < 0.05 was considered statistically significant, p-value < 0.001 was considered highly statistically significant, and p-value ≥ 0.05 was considered statistically insignificant. In our study, all, EUS, FNA cytopathology and EUS with FNA cytopathology showed high significant statistical differences in the detection of malignant cysts from benign cysts with pvalue of < 0.001, while abdominal CT/MRI imaging showed no significant difference. The diagnostic performance of EUS increased with the addition of FNA cytopathology which was more than of abdominal CT/MRI imaging. Sensitivity, specificity, PPV and NPV of abdominal CT/MRI imaging were 23.5%, 90.9%, 44.4% and 79.4% respectively, for EUS were 100%, 96.4%, 89.5% and 100% respectively, and for FNA cytopathology were 94.1%, 100%, 100% and 98.2% respectively. The accuracy of abdominal CT/MRI imaging, EUS, FNA cytopathology and EUS with FNA cytopathology were 75%, 97.2%, 98.6% and 100% respectively. Conclusion: EUS can be considered a more accurate diagnostic modality for characterization of PCLs than the abdominal CT or MRI. Addition of FNA to EUS gives a better accuracy for diagnosis and differentiation of PCLs