Over the last decade inorganic nanoparticles (NP) such as colloidal semiconductor quantum dots (QD) have been gaining increasing interest due to their unique electrical and optical properties making them valuable for future applications in electronics, medicine and biomedical imaging. However, to date there are no studies investigating the genotoxic effects of these NP in relation to their cellular uptake. A range of CdSe/ZnS QD of fixed composition but of varying size with different surface coating (carboxyl, neutral (HDA), amino groups) were used. The role of QD composition, size, shape and surface function on the kinetics of their cellular uptake and any subsequent toxic responses in human skin fibroblast (HFF-1) and lymphoblastoid (TK6) cells were also investigated using a variety of advanced imaging tools as confocal microscopy, image-based flow cytometry (ImageStream) and scanning transmission electron microscopy (STEM and TEM) coupled with EDX. Cytotoxic effects were assessed by the determination of relative population doubling assay. Induction of reactive oxygen species and mitochondrial membrane potential were also assessed and at sub cyto-toxic QD concentrations, genotoxicity was assessed using an automated micronucleus analysis system (Metafer), hprt forward gene mutation assay and pan-centromeric staining.