Transmission electron microscopy (TEM) in combination with systematic random imaging, semi-automatic image analysis and data processing has been validated for size, shape and surface topology measurements of silica nanoparticles. The accuracy of the validated TEM method was assessed by measuring two selected colloidal silica certified reference materials, ERM-FD100 and ERM-FD304. The measurement uncertainties were estimated for the modal and median particle size, shape and surface topology parameters of single primary particles. The single primary particles are distinguished from agglomerates using a linear discriminant analysis approach. After optimization of the binning process, the mode associated to the number-based particle size distribution was obtained by lognormal fitting. The methodology described in this paper, where a high level of automation of calibration, image acquisition, image analysis and data analysis is obtained, gives robust results for the modal area equivalent circular particle diameter (ECD). The expanded uncertainty of the modal ECD is estimated to be about 3 %. The largest contribution to the expanded uncertainty was found to stem from the uncertainty associated to the trueness of the TEM method.