The present study describes the detection and localization of silica particles with diameters between 2 µm and 150 nm within the cytoplasm of mammalian cells by means of ToF-SIMS 3D analysis. The particles were selected as model objects for non-luminescent, unlabeled particles that are hard to localize by other experimental approaches. ToF-SIMS analysis proved the uptake of the particles into the cell body, provided images of their distribution around the cell nucleus and indications that the cell membranes are undulated by the µm-sized particles beneath the membrane. Two ion sources (Cs+ and O2+) were applied for sputtering the organic material and expose deeper sections of the cells. The resulting images are presented and compared. Copyright © 2012 John Wiley & Sons, Ltd.