The onset of erythema nodosum, the patient’s skin lesions, is a dramatic occurrence, which inevitably brings the patient to medical attention, with or without associated findings. When uveitis is also present, sarcoidosis is the most likely diagnosis. When uveitis is absent, however, all the endemic mycoses enter into the differential diagnosis. These lesions are common in coccidioidomycosis (referred to as desert rheumatism and the bumps) and in histoplasmosis, where the sudden appearance of these lesions frequently leads to recognition of a community-wide Histoplasma outbreak. It is much less frequent in blastomycosis, but it has also been associated with outbreaks. Differentiation between sarcoidosis and endemic mycoses becomes potentially important if glucocorticosteroid therapy is contemplated. Measurement of angiotensin-converting enzyme is not helpful; it may be negative in patients with established sarcoidosis, and it may be elevated in the various acute fungal illnesses.