Among the many advantages of single-use technologies (SUTs), a low contamination rate - typically around 1% - is one of the most desirable. The unique, highly demanding performance requirements of Pichia pastoris bioprocesses (i.e., high-performance mixing and both high oxygen demand and heat transfers) have so far limited the transfer of such bioprocesses from traditional (glass or stainless steel) stirred-tank bioreactors to plastic-made single-use systems. In this chapter, we present a comprehensive guide to cultivating Pichia pastoris using the HyPerforma™ Single-Use Fermentor (SUF), a truly scalable single-use stirred tank bioreactor shown to perform comparably to conventional systems. While detailed user and software manuals are available from the manufacturer, our protocol provides additional methods and optimizations tailored to the specific needs of Pichia bioprocesses - improving the overall efficiency and effectiveness of lab-scale SUF operations.