Alien limb phenomenon refers to involuntary motor activity of a limb in conjunction with the feeling of estrangement from that limb. Alien limb serves as a diagnostic feature of corticobasal syndrome. Our objective was to determine the differential diagnoses of alien limb and to determine the features in a large group of patients with the alien limb with different underlying etiologies. We searched the Mayo Clinic Medical Records Linkage system to identify patients with the diagnosis of alien limb seen between January 1, 1996, and July 11, 2011. One hundred and fifty patients with alien limb were identified. Twenty-two were followed in the Alzheimer's Disease Research Center. Etiologies of alien limb included corticobasal syndrome (n = 108), stroke (n = 14), Creutzfeldt Jakob disease (n = 9), hereditary diffuse leukoencephalopathy with spheroids (n = 5), tumor (n = 4), progressive multifocal leukoencephalopathy(n = 2), demyelinating disease (n = 2), progressive dementia not otherwise specified (n = 2), posterior reversible encephalopathy syndrome (n = 1), corpus callosotomy (n = 1), intracerebral hemorrhage (n = 1) and thalamic dementia (n = 1). Ten of 14 cerebrovascular cases were right hemisphere in origin. All cases involved the parietal lobe. Of the 44 patients with corticobasal syndrome from the Alzheimer's Disease Research Center cohort, 22 had alien limb, and 73 % had the alien limb affecting the left extremities. Left sided corticobasal syndrome was significantly associated with the presence of alien limb (p = 0.004). These findings support the notion that the alien limb phenomenon is partially related to damage underlying the parietal cortex, especially right parietal, disconnecting it from other cortical areas.