The development of novel engineered nano-sized materials is a rapidly emerging technology with many applications in medicine and industry. In vitro and in vivo studies have suggested many deleterious effects of carbon nanotube exposure including granulomatous inflammation, release of cytosolic enzymes, pulmonary fibrosis, reactive oxygen damage, cellular atypia, DNA fragmentation, mutation and errors in chromosome number as well as mitotic spindle disruption. The physical properties of the carbon nanotubes make respiratory exposure to workers likely during the production or use of commercial products. Many of the investigations of the genotoxicity of carbon nanotubes have focused on reactive oxygen mediated DNA damage; however, the long thin tubular-shaped carbon nanotubes have a striking similarity to cellular microtubules. The similarity of carbon nanotubes to microtubules suggests a potential to interact with cellular biomolecules, such as the mitotic spindle, as well as the motor proteins that separate the chromosomes during cell division. Disruption of centrosomes and mitotic spindles would result in monopolar, tripolar, and quadrapolar divisions of chromosomes. The resulting aneuploidy is a key mechanism in the potential carcinogenicity of carbon nanotubes.