Here we report the extreme toxicity in vitro of Bi(OH)3and α-Bi2O3nanoparticles (NPs), obtained through a facile synthesis with an average single particle size of 6–10 nm, tested on malignant gliosarcoma 9L and MCF-7 human breast cancer cells. For both nanomaterials, clonogenic assays reveal a mortality of over 90% in 9L and MCF-7 cells for a concentration of 50 μg/mL after incubation for 24 h. Moreover, the NPs show a significant mortality of up to 60% in the malignant cells at the very low concentration of 6.25 μg/mL. In contrast, at the same concentration, the nanomaterials exhibit no noticeable mortality towards normal Madin-Darby canine kidney cells. The internalisation of the NPs was demonstrated using flow cytometry and confocal microscopy was used to investigate when the loss of cell viability starts. The NPs show a faster cell death in 9L cells compared with MCF-7 cells, demonstrated via the identification of apoptosis through increased sub G1levels after 24 h of NP incubation. Cleavage is identified as the main apoptotic nuclear morphology in 9L, which suggests the presence of reactive oxygen species.