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An isolated pyogenic pancreatic abscess (IPPA) without pancreatitis is extremely rare but can occur in patients with uncontrolled diabetes. This pathologic condition poses a clinical challenge in diagnosis and management because it can be confused easily with a malignancy. Endoscopic ultrasound (EUS) may be a useful diagnostic modality for indeterminate pancreatic lesions and IPPA. Here, we report two cases with elevated carbohydrate antigen 19-9 levels and pancreatic masses on cross sectional imaging. The patients were subsequently diagnosed with IPPA by EUS. EUS-guided drainage was performed successfully and the patients’ clinical symptoms and radiologic findings improved. In our experience, EUS and EUS-guided drainage are crucial steps for the diagnosis and management of patients with an indeterminate pancreatic lesion. In addition, EUS-guided drainage has excellent technical and clinical outcomes for the treatment of IPPA.