Abstract: Embodiments of a system, method, and kit for visualizing a nucleus are disclosed. A tissue sample is pretreated with a protease to permeabilize the nucleus, and then incubated with a nanoparticle/DNA-binding moiety conjugate. The DNA-binding moiety includes at least one DNA-binding molecule. The conjugate binds to DNA within the nucleus, and the nanoparticle is visualized, thereby visualizing the nucleus. Computer and image analysis techniques are used to evaluate nuclear features such as chromosomal distribution, ploidy, shape, size, texture features, and/or contextual features. The method may be used in combination with other multiplexed tests on the tissue sample, including fluorescence in situ hybridization. Kits for performing the method include a protease enzyme composition, a nanoparticle/DNA-binding moiety conjugate, and a reaction buffer.