 This paper presents a new technique for analyzing proteomes from single cells with high sensitivity and accuracy. The technique combines miniaturized sample preparation, low flow rate chromatography, and a novel trapped ion mobility mass spectrometer to achieve greater than 10 times higher sensitivity compared to existing methods. This enables precise quantification of proteomes and their changes in single, FACS isolated cells. It also reveals unexpected proteins and allows cell phase prediction. Compared to transcriptomic analysis, this technique shows a stable core proteome despite perturbations, suggesting that the core proteome is more stable than previously thought. This technology can be used to analyze proteomes from small cell counts, allowing researchers to gain unprecedented insight into cellular heterogeneity in health and disease. This article was authored by Andreas David Bruner, Marvin Thielet, Catherine Vassilopoulou, and others.