Although carcinoma of the head of the pancreas and chronic pancreatitis are usually easy to distinguish on clinical presentation and subsequent investigation, there can be enough overlap in the presenting features and on imaging studies that differentiation is sometimes extremely difficult. As this confusion may lead to either major pancreatic resection for benign disease, or rejection of surgery for a potentially curable lesion, all attempts to arrive at a correct diagnosis should be pursued. This article provides an update of investigative techniques in pancreatic disease, and offers an algorithm for the clinical approach to the patient who appears to present with this diagnostic and therapeutic dilemma.