Blastomycosis can only be diagnosed through the identification of the yeasts of Blastomyces dermatitidis in body fluids, tissues, or cultured material. The charts from 123 patients treated for blastomycosis at the University of Mississippi Medical Center from January 1980 through May 2000 were reviewed to determine the role of wet preparation, cytology, histology, and culture in diagnosing this fungal disease. Cytology uncovered the etiologic agent in 56.1% of all cases and in 71.8% of pulmonary cases. Cytology also was the first method to disclose the fungus in 57.7% of pulmonary cases. Sputum was the cytology specimen examined in 51% of the patients. In 69 patients with lung involvement, pulmonary cytology was positive in 97% of cases. Wet preparation was the second method to most commonly uncover the fungus in 37.4% of all cases. Histology was the third method with 32.5% of positive cases. Cultures were positive in 64.2% of all cases but they were the first to detect the fungus in only 3.2% of all patients. There was pulmonary involvement in 87% of patients, cutaneous involvement in 20%, osseous involvement in 15%, and central nervous involvement in 3%. In the medical literature the relative proportion of pulmonary versus disseminated disease clearly increased in series reported after 1959. Proportionally to the pattern of patients admitted to the University of Mississippi Medical Center, there is a clear predominance of black males among patients with blastomycosis followed by black females. White females constitute the sex/ethnic group least affected by this fungal disease.