Despite its usefulness in adults with cerebral gliomas, indications for thallium-201 single-photon emission computed tomography (SPECT) in pediatric brain tumor patients are not well defined. We prospectively compared thallium SPECT with gadolinium-enhanced MR (Gd-MR) to determine if thallium SPECT provides clinically useful information that cannot be derived from Gd-MR. We studied 24 pediatric brain tumor patients, 7 at presentation and 17 during therapy. MR imaging included T2 and pre- and postgadolinium T1 images. Thallium SPECT was done within 48 h of MR imaging; thallium indices were calculated for 12 of 14 lesions which showed thallium uptake. Surgery and/or clinical follow-up are available in all patients. The tumors included pilocytic astrocytoma (7), medulloblastoma (5), brainstem glioma or glioblastoma (4), germinoma (3), optic glioma (2), mixed glioma (1), primitive neuroectodermal tumor (1), and choroid plexus carcinoma (1). Among the primary tumors, compared to MR, thallium SPECT was false-negative for tumor in 1 patient and true-positive in 6 patients. Among the patients studied while on therapy, compared to MR, thallium SPECT was true-negative for tumor in 7, true-positive in 5, false-negative in 3, and false-positive in 2. In both groups of patients, thallium SPECT underestimated tumor burden as nonenhancing regions of the tumors were not thallium-avid. Thallium indices did not correlate with histologic grade, biologic aggressiveness, or tumor type. We were unable to establish indications for the use of thallium SPECT in this setting as there was little clinically useful information derived from thallium SPECT that was not provided by Gd-MR.