False diagnosis of autoimmune diseases may have many different reasons. It may be caused by the relative rareness of these rather complicated diseases, by sometimes mono- or oligosymptomatic courses, and by the highly variable clinical presentations. In addition, many physicians lack experience in the treatment of these rheumatologic-immunological diseases. A first shot diagnosis, inadequate technique in obtaining a correct history or in performing a physical examination, as well as an incomplete evaluation of differential diagnosis, are possible causes of wrong diagnosis in the context of autoimmune diseases and may delay effective therapy. To illustrate these problems, three examples of patients with autoimmune diseases are discussed, namely a patient with polyarthritis and fever, a patient with polymyalgia rheumatica, and a patient with an ulcerative skin lesion. These examples serve to discuss the difficulty of correct diagnosis in complicated courses of autoimmune diseases, which are also relatively common in general practice.