Background: Cross-resistance to medical azoles by exposure to azole pesticides is well documented forAspergillusfamily fungi but is poorly evaluated for other environmental pathogen fungi, particularly for yeasts belonging to theCryptococcus neoformans/Cryptococcus gattiispecies complexes. Methods: One thousandC. neoformansyeast were exposed to various concentrations of seven different commonly used azole pesticides. Clones surviving exposure were picked randomly, and their minimal inhibitory concentrations (MICs) of fluconazole, voriconazole, posaconazole, itraconazole and isavuconazole were assessed. Results: Depending on the pesticide used for exposure, up to 13.3% of selectedCryptococcuscolonies showed a phenotype of resistance to fluconazole, and among them, several showed cross-resistance to another or several other medical azoles. Molecular mechanisms involved in the resistance setups seem to be dependent on ERG11 and AFR1 gene overexpression. Conclusion: Exposure to any of the seven azole pesticides tested is capable of increasing the MIC of fluconazole inC. neoformans, including up to the level of the fluconazole-resistant phenotype, as well as generating cross-resistance to other medical azoles in some cases.