A major limitation of SIMS studies of cells is the limited number of molecules available for detection. This study examines the possibility of utilizing a molecular tag that is easily identifiable using SIMS and does not interfere with the mass spectra of commonly identified cellular components, to aid in the visualization of specific cellular organelles. Here, a fluorescent, nuclear stain (Hoechst 33342) was used to allow for verification of the staining protocols prior to SIMS analysis. The stain was successfully chemically imaged within the nuclear region of a glutaraldehyde-fixed bovine aortic endothelial cell. The ability to chemically map a larger variety of organelles and cellular components will allow for further possible study of a greater number of biological pathways and processes, as well as make cell–drug studies more feasible using SIMS. Copyright © 2014 John Wiley & Sons, Ltd.