Resection for suspected high-grade pancreatic intraepithelial neoplasia (hg-panIN) shows a significant rate of benign lesions and small invasive carcinomas, underscoring the need for cautious decision-making.

• In a study of 94 patients, 27.7% had benign lesions, 46.8% had carcinoma in situ, and 25.5% were diagnosed with invasive carcinoma.
• Even with radiological findings typical for hg-panIN, 22.2% were benign and 25.4% were invasive carcinoma.
• The positive predictive value of pancreatic juice cytology was high at 96.7%, but 61.5% of cytology-negative cases still revealed malignancy.

Surgeons must carefully consider surgical indications given the potential for substantial misdiagnosis in these patients.