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This study investigated the combined capability of thallium-201 (Tl)-SPECT and fluorine-18-fluoro-deoxy-glucose (FDG)-PET for differential diagnosis of posterior fossa brain tumors using multiple discriminant analysis.This retrospective study was conducted under approval of the institutional review board. In the hospital information system, 27 patients with posterior fossa intra-axial tumor between January 2009 and June 2015 were enrolled and grouped as the following 7 entities: low grade glioma (LGG) 6, anaplastic astrocytoma (AA) 2, glioblastoma (GBM) 3, medulloblastoma (MB) 3, hemangioblastoma (HB) 6, metastatic tumor (Mets) 3, and malignant lymphoma (ML) 4. Tl and FDG uptakes were measured at the tumors and control areas, and several indexes were derived. Using indexes selected by the stepwise method, discriminant analysis was conducted with leave-one-out cross-validation.The predicted accuracy for tumor classification was 70.4% at initial analysis and 55.6% at cross-validation to differentiate 7 tumor entities. HB, LGG, and ML were well-discriminated, but AA was located next to LGG. GBM, MB, and Mets largely overlapped and could not be well distinguished even applying multiple discriminant analysis. Correct classification in the original and cross-validation analyses was 44.4% and 33.3% for Tl-SPECT and 55.6% and 48.1% for FDG-PET.