BACKGROUND: Inferior Fronto-Occipital Fascicle (IFOF) is a multitasking connection bundle essential for communication and high level mentalization. The aim of the present study was to quantitatively assess its radiological-anatomical-morphometric modifications according to different brain tumor histotype. METHODS: A retrospective multicentric Italian study was conducted. IFOF reconstructions were calculated for both hemispheres for each patient diagnosed with Glioblastoma (GBM), Low Grade Glioma (LGG), Brain Metastasis and Meningioma using Elements Fibertracking software (Brainlab AG). A 3D object of each fascicle was evaluated for volume, average fractional anisotropy (FA) and length. The cerebral healthy hemisphere was compared to the pathological contralateral in different tumor histotype. RESULTS: 1294 patients were evaluated. 156 met the inclusion criteria. We found a significant difference between healthy hemisphere and the contralateral for IFOF mean length and volume (p-value < 0.001). Considering GBM subgroup, Student's t-test confirmed the results. In LGG subgroup, there was significant difference between the 2 hemispheres for IFOF mean length, mean FA and volume (respectively p-value 0.011; p-value 0.021, p-value < 0.001). In patients affected by brain metastasis (18) Student's t-test showed a significant difference for FA and volume (p-value 0.003 and 0.02 respectively). No differences were found in patients affected by meningiomas. CONCLUSIONS: The careful preoperative neuroradiological evaluation of the brain-tumor interface is indispensable to plan a tailored surgical strategy and perform a safe and effective surgical technique. It depends on the tumor histology and pattern of growth. GBM have a mixed component, with the solid enhancing nodule which accounts for IFOF displacement and the peritumoral area which accounts for an infiltrative/destructive effect on the fascicle. LGG determine a prevalent infiltrative pattern. Metastases determine an IFOF dislocation due to peritumoral oedema. Meningiomas do not impact on WM anatomy.