Cells have a rich inner structure that is commonly explored by microscopy. Classical biochemical methods that break apart the cells and fractionate them along a gradient have now gotten a new lease on life through modern methods of mass spectrometry-based proteomics. Their common principle is to comprehensively measure all the proteins in each of the fractions. The resulting quantitative profile then associates thousands of proteins to their cellular homes. Here, the author recounts how protein correlation profiling, the first such technique, was conceived and how it was applied to answer intricate cell biological questions.