The role of diagnostic laparoscopy in patients with periampullary and pancreatic malignancies is controversial. A retrospective review was performed including all patients (n = 188) with a periampullary or pancreatic malignancy who underwent both CT and laparotomy at our institution between January 1997 and December 1999. The overall resectability rate for all periampullary cancers was 67.3% (115 of 171 patients). This compared favorably with the resectability rate for cancers of the pancreatic body and tail (3 of 17 patients, 17.6%; P < 0.01 vs. periampullary cancers). Fifty percent of patients with periampullary cancers were unresectable because of metastatic disease, whereas metastatic disease precluded resection in 64.3% of patients with cancers of the pancreatic body and tail. After patients undergoing operative palliation were eliminated, a nontherapeutic laparotomy would have been precluded by the use of diagnostic laparoscopy in only 2.3% of patients with periampullary cancers (4 of 171 patients). In contrast, 6 (35.3%) of 17 patients with cancers of the pancreatic body and tail underwent a nontherapeutic laparotomy (P < 0.01 vs. periampullary cancers). One hundred fifty-eight (84%) of the 188 CT reports reviewed could be definitively categorized as either "likely to be resectable" or "likely to be unresectable." The remaining 16% were equivocal. Of the 107 patients categorized as likely to be resectable, 89 were actually resected (83.2%). In contrast, only 10 of the 51 patients categorized as likely to be unresectable could be resected (19.6%).