The chameleon is an industry-enabling sample-preparation system for cryo-electron microscopy. The new system has been designed to enable consistent application of samples to high-quality foil grids for cryo-EM analysis, automating the current standard approach, which is a technically demanding, largely manual process. Based on the academically developed Spotiton instrument conceived at the New York Structural Biology Center, chameleon represents the next generation of sample-preparation solutions for cryo-EM. This can allow researchers in the rapidly growing field to more easily and accurately determine the structure of biomolecules, supporting protein research and drug discovery. The new system can bring significant improvements to current sample-prep workflows, including high-speed blot-free plunging, automated grid handling, and grid screening based on ice thickness.