The pathogenesis of histoplasmosis in humans is similar to that in dogs and cats.

Clinical presentations of histoplasmosis in humans include:

• acute and chronic pulmonary disease
• "histoplasmomas" (healed pulmonary nodules)
• mediastinal granulomatosis and lymphadenitis
• ulcerative cutaneous lesions
• Progressive disseminated histoplasmosis occurs in immunocompromised patients, sometimes with remarkable oral ulcers.

A large-scale outbreak of pulmonary histoplasmosis occurred among visitors to Acapulco, Mexico in March 2001, most of whom stayed at a particular hotel. Since then, two additional outbreaks of histoplasmosis have occurred in association with the same hotel.

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