PURPOSE:We applied voxelwise apparent diffusion coefficient (ADC) histogram analysis in addition to structural magnetic resonance imaging (MRI) findings and patients' age for differentiation of intraaxial posterior fossa tumors involving the fourth ventricle. PARTICIPANTS AND METHODS:Pretreatment MRIs of 74 patients with intraaxial brain neoplasm involving the fourth ventricle, from January 1, 2004 to December 31, 2015, were reviewed. The tumor solid components were segmented and voxelwise ADC histogram variables were determined. Histogram-driven variables, structural MRI findings, and patient age were combined to devise a differential diagnosis algorithm. RESULTS:The most common neoplasms were ependymomas ( n = 21), medulloblastoma ( n = 17), and pilocytic astrocytomas ( n = 13). Medulloblastomas followed by atypical teratoid/rhabdoid tumors had the lowest ADC histogram percentile values; whereas pilocytic astrocytomas and choroid plexus papillomas had the highest ADC histogram percentile values. In a multivariable multinominal regression analysis, the ADC 10th percentile value from voxelwise histogram was the only independent predictor of tumor type ( p < 0.001). In separate binary logistic regression analyses, the 10th percentile ADC value, tumor morphology, enhancement pattern, extension into Luschka/Magendie foramina, and patient age were predictors of different tumor types. Combining these variables, we devised a stepwise diagnostic model yielding 71%25 to 82%25 sensitivity, 91%25 to 95%25 specificity, 75%25 to 78%25 positive predictive value, and 89%25 to 95%25 negative predictive value for differentiation of ependymoma, medulloblastoma, and pilocytic astrocytoma. CONCLUSION:We have shown how the addition of quantitative voxelwise ADC histogram analysis of the tumor solid component to structural findings and patient age can help with accurate differentiation of intraaxial posterior fossa neoplasms involving the fourth ventricle based on pretreatment MRI.