The Great Imitator (also the Great Masquerader) is a phrase used for medical conditions that feature nonspecific symptoms and may be confused with a number of other diseases. The term connotes especially difficult differential diagnosis, increased potential for misdiagnosis, and the protean nature of some diseases. Most great imitators are systemic in nature or have systemic sequelae, and an aspect of nonspecific symptoms is logically almost always involved. In some cases, an assumption that a particular sign or symptom, or a particular pattern of several thereof, is pathognomonic turns out to be false, as the reality is that it is only nearly so.
As recently as the 1950s, syphilis was widely considered by physicians to be "the great imitator", and in the next few decades after that, several other candidates, mainly tuberculosis but occasionally others, were asserted as being "the second great imitator". But because differential diagnosis is inherently subject to occasional difficulty and to false positives and false negatives, the idea that there are only one or two great imitators was more melodrama than objective description. In recent decades, more than a dozen diseases have been recognized in the medical literature as worthy of being considered great imitators, on the common theme of recurring misdiagnoses/missed diagnoses and protean manifestations. Nonetheless, not every caveat (not every mimic) meets the threshold, because it is inherent to differential diagnosis generally that there are thousands of caveats.