This article experimentally examines methods for implementing the philosophies of Lean Six Sigma (LSS) in a High-Mix Low-Volume (HMLV) manufacturing environment. HMLV environments present unique challenges to LSS paradigms because of the need for extraordinary operational flexibility and customer responsiveness. The subject HMLV manufacturer for this experimentation manufactures (among 8500 others) an example component for which 3 machines work independently to perform the necessary operations to manufacture this component. The experiment that is the subject of this research seeks to adapt LSS philosophies to develop treatments to improve the performance of the manufacturing of this component. These LSS-inspired treatments included 1) using cellular manufacturing methods, and the 3 machines as a single work cell to manufacture the component, and 2) using a single multipurpose machine to perform all operations required to manufacture the component. The results of this experiment demonstrate that the cellular manufacturing method was the most effective to reduce costs, to standardize operations at a process level, and to increase throughput. The single machine processing method improved production rates and on-time delivery relative to the baseline, but greatly increased lead time, thereby increasing total cost per part. These results highlight the importance of critically assessing the application of LSS within HMLV environments compared to the Low-Mix High-Volume (LMHV) environments where LSS is traditionally successful. HMLV manufacturers and researchers can use these findings to identify the most effective methods for their specific needs and to design interventions that will improve system-level manufacturing performance in high mix environments.