Blastomycosis is a uncommonly diagnosed but important fungal infection in the south-central and midwestern United States. Epidemics related to a point-source exposure includes patients of all ages and both sexes, but endemic cases are usually in young to middle-aged adults, more reported commonly in men than women. The infection may mimic many other more common illnesses. Pneumonia is the most common manifestation, and the lung is almost always the organ initially infected. Infection in the lung may present either mimicking a short term bacterial pneumonia or a more indolent and long-term condition like tuberculosis or lung cancer. Cutaneous disease is the most common site of extrapulmonary involvement and may present with verrucous or ulcerative lesions. Osseous, prostatic, and central nervous system involvement are next most frequent in descending order. In a patient from the proper endemic area, blastomycosis should be on the differential diagnostic list for lung, skin, and other organ system infection.