A literature search revealed only five recent articles with specific information on the incidence of performance of pancreaticoduodenectomy when the preoperative diagnosis is uncertain. The collected incidence of benign diagnoses in the five papers was 13.1%. Five other papers describing patients from before 1990 reported rates of benign diagnoses of 9.7%, p<0.007 compared to the more recent series. The introduction of advanced diagnostic tests has not decreased the incidence of benign pathology after pancreaticoduodenectomy for presumed cancer. Pancreaticoduodenectomy should be performed without a definitive diagnosis of cancer if, in the opinion of an experienced surgeon, clinical suspicion is high.