Clinical diagnostic medicine requires a structured approach to complete a differential diagnosis and subsequent rule in / rule out data analysis. In pursuit of a diagnosis of pulmonary embolism (PE), many competing diagnoses may mimic the presentation. A deft understanding and clarity of diagnosis are needed to work through these competing diagnoses to arrive at the correct conclusion. This chapter strives to discuss patient presentations that mimic each other that make the identification of PE difficult when PE is present and the diagnoses that may be present when PE is not. Mastery of the information in this chapter is designed to leave the reader better informed to arrive at the correct diagnosis as promptly as possible to provide correct and timely care whether a PE is present or another problem is responsible for the presenting symptoms. Please take time to consider the subtleties herein as the differences may seem trivial but, actually, illustrate the art of diagnosis.