Although the use of synthetic amorphous silica (SAS) is steady increasing, scarce information exists on its potential health risk. In particular few and conflictive data exist on its genotoxicity. To fill in this gap we have used Drosophila melanogaster as in vivo model test organism to detect the genotoxic activity of different SAS with different primary sizes (6, 15, 30 and 55 nm). The wing-spot assay and the comet assay in larvae haemocytes were used, and the obtained results were compared with those obtained with the microparticulated form (silicon dioxide). All compounds were administered to third instar larvae at concentrations ranging from 0.1 to 10 mM. No significant increases in the frequencies of mutant spots were observed in the wing-spot assay with any of the tested compounds. On the other hand, significant dose-dependent increases in the levels of primary DNA damage, measured by the comet assay, were observed for all the SAS evaluated but mainly when high doses (5 and 10 mM) were used. These in vivo results contribute to increase the database dealing with the potential genotoxic risk associated to SAS nanoparticles exposure. (C) 2014 Elsevier B.V. All rights reserved.