Imaging mass spectrometry (IMS) can produce thousands of ion images, providing molecular context to classical histological analysis. New LC-MS proteomics methodologies that have single-cell level sensitivity can now be extended to quantitative proteome mapping using a “voxelation” approach. This has resulted in a depth of proteome coverage and robust quantitation superior to those of existing IMS platforms. The application of this innovative platform to proteome mapping clearly demonstrates the exciting potential of proteome imaging to advance biomedical research.