Recent molecular studies suggest that Cryptococcus may inhabit the normal human mouth. We attempted to isolate Cryptococcus from 21 adult non-acutely ill patients and 40 volunteer medical and non-medical staff in Southeastern Wisconsin, USA. An upper lip sulcus culture and an oral rinse specimen were inoculated separately onto Staib (birdseed) agar containing chloramphenicol and incubated in gas impermeable zip lock bags at 35 °C. No cryptococci were grown from any of the 122 samples from the 61 subjects. Both specimens from a woman with no risk factors for fungal disease yielded a black yeast at 4 days on Staib agar. This isolate was shown to be Exophiala dermatitidis by colony and microscopic morphology, analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and sequencing through the internal transcribed spacer ribosomal RNA gene. This appears to be a novel isolation of E. dermatitidis from the oral cavity of a generally healthy human.