In view of the increasing number of new imaging techniques and serum tumor markers, it is not well established which combination or which order of tests may provide the most information for diagnosis of pancreatic carcinoma. This review determines the diagnostic value of the various tests and evaluates which combination of tests may provide the most information and what may be considered to be a current rational approach to the diagnosis of pancreatic carcinoma. In the present analysis endoscopic retrograde chol-angiopancreatography (ERCP) provided a 92% sensitivity that exceeded the 83% and 74% sensitivities calculated for computed tomography (CT) and ultrasound, respectively. The specificity of all three imaging techniques exceeded 90%. Serum determination of CA 19–9 yielded an 83% sensitivity, which was considerably higher than sensitivities of carcinoembryonic antigen and various other tumor markers. The combination of CA 19–9 and ultrasound improved the sensitivity of each test performed alone by 10–15%. Fine-needle biopsy allows diagnosis of pancreatic carcinoma with a sensitivity of 83% and an almost perfect specificity of 99%. On the basis of these data, the combination of ultrasound and determination of CA 19–9 is recommended as the initial tests when pancreatic carcinoma is suspected. CT also must be performed if ultrasound is indeterminant or inconsistent with the clinical evaluation, as well as in patients with negative ultrasound but abnormal CA 19–9. Negative results of CT, ultrasound, and CA 19–9 will exclude pancreatic carcinoma in most patients. A positive ultrasound or CT result usually leads to fine-needle biopsy, which helps avoid most diagnostic laparotomies. ERCP must be performed in patients where ultrasound, CT, and fine-needle biopsy do not clarify the diagnosis. In the majority of patients with pancreatic carcinoma, noninvasive imaging techniques such as ultrasound and CT also allow adequate staging. In some patients, however, laparoscopy and angiography may need to be performed for strategic planning of further therapy. Although modern imaging techniques and serum tumor markers allow diagnosis of pancreatic carcinomas as small as 2–3 cm and help avoid most diagnostic laparotomies, this improvement in diagnostic capability has as yet not significantly improved the prognosis.