BACKGROUND: Contrast enhanced harmonic endoscopic ultrasound (CEH-EUS) is a spreading technique; some studies have shown its value in the diagnosis of pancreatic adenocarcinoma using quantitative analysis. AIM: To examine the value of CEH-EUS for differentiating various pancreatic lesions in everyday routine with qualitative and quantitative analysis. METHODS: Data of 55 patients with pancreatic lesions who underwent CEH-EUS were analysed retrospectively. Perfusion characteristics were classified by the investigator qualitatively immediately upon investigation, quantitative analysis was performed later on. Samples from fine needle aspiration (EUS-FNA) or surgical specimen served as gold standard. RESULTS: CEH-EUS showed 39 hypoenhanced lesions, 3 non-enhanced and 13 hyperenhanced lesions. Concordance of the investigators qualitative classification of peak contrast enhancement with quantitative analysis later on was 100%, while other parameters such as arrival time, time to peak or area under the curve did not show additional value. 34 of 39 hypoenhanced lesions were pancreatic adenocarcinoma; of the hyperenhanced lesions 4 were inflammatory, 3 neuroendocrine carcinomas, 1 lymphoma, 1 insulinoma and 4 metastases (2 of renal cell carcinoma, 2 of lung cancer). Non-enhanced lesions showed up as necroses. Sensitivity for the detection of pancreatic adenocarcinoma was 100%, specificity 87.2% for hypoenhancement alone; in otherwise healthy pancreatic tissue all hypoenhanced lesions were pancreatic adenocarcinoma (sensitivity and specificity 100%, PPV and NPV for adenocarcinoma 100%). CONCLUSION: This study again shows the excellent value of CEH-EUS in everyday routine for diagnostics of various focal pancreatic lesions suggesting that qualitatively assessed hypoenhancement is highly predictive for adenocarcinoma. Additional quantitative analysis of perfusion parameters does not add diagnostic yield. In case of the various hyperenhanced pancreatic lesions in our data set, histologic sampling is essential for further treatment.