Cryptococcal pleuritis is rare in individuals with no underlying disease. We report a case of pulmonary cryptococcosis followed by pleuritis in a patient on fluconazole treatment. Biopsy of the pleura revealed a granuloma and a cryptococcal body, while PCR and sequence analysis of extracted DNA from the pleura proved the presence of Cryptococcus species, most likely C. neoformans. Voriconazole with flucytosine and drainage of the pleural effusion were effective in treating the patient.