Recently, there has been a major thrust to understand biological processes at the nanoscale. Optical microscopy has been exceedingly useful in imaging cell microarchitecture. Characterization of cell organization at the nanoscale, however, has been stymied by the lack of practical means of cell analysis at these small scales. To address this need, we developed a microscopic spectroscopy technique, single-cell partial-wave spectroscopy (PWS), which provides insights into the statistical properties of the nanoscale architecture of biological cells beyond what conventional microscopy reveals. Coupled with the mesoscopic light transport theory, PWS quantifies the disorder strength of intracellular architecture. As an illustration of the potential of the technique, in the experiments with cell lines and an animal model of colon carcinogenesis we show that increase in the degree of disorder in cell nanoarchitecture parallels genetic events in the early stages of carcinogenesis in otherwise microscopically/histologically normal-appearing cells. These data indicate that this advance in single-cell optics represented by PWS may have significant biomedical applications.light-scattering spectroscopy ͉ nanoarchitecture ͉ subdiffusion E xisting knowledge of changes in cell architecture in disease processes is based to a large degree on the histological examination of cells and tissue. On the other hand, it is well accepted that histological and, thus, microarchitectural, aberrations are preceded by molecular, genetic, or epigenetic changes. One may pose a question whether these events are still accompanied by alterations in cell architecture that are histologically undetectable. Indeed, the diffraction limit restricts the resolution of conventional light microscopy to, at best, 200 nm. This is larger than the sizes of the fundamental building blocks of the cell, such as membranes, cytoskeleton, ribosomes, and nucleosomes. Thus, conventional light microscopy is insensitive to changes in nanoarchitecture, which is the fundamental basis of cell organization. It is clear that the fact that a cell is histologically normal may not necessarily be equated with the cell not having nanoscale structural alterations. Cellular alterations in carcinogenesis provide an illustrative and practically important example. The process of carcinoma formation involves stepwise accumulation of genetic and epigenetic alterations in epithelial cells over a time period of many years. Dysplasia, or structural alterations detectable by microscopy, is a relatively late event in this process. From a cancerresearch perspective, it is important to recognize the earlier stages of carcinogenesis that precede histological changes. One can hypothesize that although these genetic/epigenetic aberrations have not yet resulted in histologically apparent changes, they may still be accompanied by architectural consequences that occur at the nanoscale.Therefore, it is of major importance to design optical techniques for inspecting cell nanoarchitecture. One approach to...