Fungal infections are an increasingly serious problem in light of advances in modern medical practices and immunosuppressive diseases. Resistance to frequently administered antifungal drugs, such as azoles, is steady increasing. In the human fungal pathogen Candida albicans the evolution of drug resistance is driven by phenotypic variability, its underlying DNA mutations and by a high degree of genomic plasticity. A particularity of C. albicans stress response repertoire is the ability to vary the levels of leucine and serine at CUG positions on a genome wide scale. Here we show that increased levels of mistranslation, like in bacteria, hasten the appearance of drug tolerance and resistance in the eukaryote C. albicans by accelerating genome diversification