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 (DDx), 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 DDx caveat (not every mimic) meets the threshold, because it is inherent to DDx generally that there are thousands of caveats (thousands of instances of the theme, "be careful to rule out X before diagnosing Y"); for example, ectopic pregnancy and ovarian neoplasia can mimic each other, as can myocardial infarction and panic attack, but they are not established as great imitators per se (rather, merely DDx considerations). The list of great imitators here relies on references in the medical literature applying that label, or on other references documenting a condition's especially recurrent and poignant reputation for misdiagnoses. Conditions or diseases sometimes referred to with this nickname thus include the following:

Low blood sugar

Tumors (neoplasms), especially cancerous tumors or any endocrine tumors

Vitamin deficiency

Substance abuse

Rheumatic diseases (most with autoimmune components)

Dysplastic diseases, some with precancerous or rheumatologic aspects

Neurologic disorders

Gut diseases

Abdominal inflammations or their mimics

Endocrine disorders

Thromboembolic events or their mimics

Infectious diseases

Breathing-related sleep disorders (sleep-disordered breathing)

Proteinopathies

Mass effect inside the cranium

Skin conditions