Author SummaryThe capacity of the yeast Candida albicans to grow in several cellular forms—a phenomenon known as phenotypic plasticity—is critical for its survival and for its ability to thrive and cause infection in the human host. In this study, we report a novel form of C. albicans, the “gray” phenotype, which may enhance fitness and confer an adaptive advantage for this important pathogenic yeast in certain host environments. The gray cell type, together with the previously discovered “white” and “opaque” cell types, forms a tristable phenotypic switching system. The three phenotypes differ in their cellular and colony appearance, their global transcriptional profiles, their production of secreted aspartyl proteinases (enzymes that degrade host tissues and release nutrients), and their virulence in different infection models. Moreover, gray cells exhibit a level of mating competency that is intermediate between that of white and opaque cells. We further demonstrate that two key transcriptional regulators, Wor1 and Efg1, play central roles in the regulation of the “white-gray-opaque” tristable transitions. Our study reveals a multi-stable and heritable switching system, indicating that the adoption of distinct morphological forms in response to environmental change could be much more elaborate than previously thought.