Chemical agents routinely used in neurosurgery to achieve intraoperative hemostasis can cause a foreign body reaction, which appears on magnetic resonance (MR) images to be indistinguishable from recurrent tumor. Clinical and/or imaging evidence of progression of disease early after surgical resection or during aggressive treatment may actually be distinct features of granuloma in these circumstances. A series of three cases was retrospectively analyzed for clinical, imaging, surgical, and pathological findings, and the consequences they held for further disease management. All patients were boys (3, 3, and 6 years of age, respectively) and all harbored primitive neuroectodermal tumors. Two tumors were located in the posterior fossa and one was located in the right parietal lobe. Two boys exhibited clinical symptoms, which were unexpected under the circumstances and prompted new imaging studies. One patient was asymptomatic and imaging was performed at planned routine time intervals. The MR images revealed circumscribed, streaky enhancement in the resection cavity that was suggestive of recurrent disease. This occurred 2 to 7 months after the first surgery. At repeated surgery, the resected material had the macroscopic appearance of gelatin sponge in one case and firm scar tissue in the other cases. Histological analysis revealed foreign body granulomas in the resected material, with Gelfoam or Surgicel as the underlying cause. No recurrent tumor was found and the second surgery resulted in imaging-confirmed complete resection in all three patients. Because recurrent disease was absent, the patients continued to participate in their original treatment protocols. All patients remain free from disease 34, 32, and 19 months after the first operation, respectively. During or after treatment for a central nervous system neoplasm, if unexpected clinical or imaging evidence of recurrence is found, a second-look operation may be necessary to determine the true nature of the findings. If the resection yields recurrent tumor, additional appropriate oncological treatment is warranted, but if a foreign body reaction is found, potentially harmful therapy can be withheld or postponed.