Ki67 (also known as MIB) is a monoclonal antibody staining agent, which is routinely used as a marker of cellular proliferation. It is used to evaluate the proliferative potential of malignant tumors, since it is thought to stain only those cells undergoing active division. The paradoxical elevation of the Ki67 labeling index observed in radiosurgically treated benign and malignant tumors is reported. Ten patients, who had previously undergone either linac or Gamma Knife radiosurgery, underwent surgical resection for a radiographically quiescent tumor. One patient underwent autopsy after dying from complications of radiosurgery. All were thought to be suffering from adverse radiation effect (ARE) and were refractory to conservative management. None were thought to have a recurrent tumor. All of the resected tumors were subjected to analysis with Ki67 staining. Despite the radiographic stability of the tumors, all manifested significantly elevated populations of cells exhibiting positivity for Ki67 antigen. This staining pattern would suggest a significant proliferative potential, which did not match the observed clinical course. The literature is reviewed and possible mechanisms to explain the paradoxical findings are presented.