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BACKGROUND The literature on white matter anatomy underlying the human orbitofrontal cortex (OFC) is scarce in spite of its relevance for glioma surgery. OBJECTIVE To describe the anatomy of the OFC and of the underlying white matter fiber anatomy, with a particular focus on the surgical structures relevant for a safe and efficient orbitofrontal glioma resection. Based on anatomical and radiological data, the secondary objective was to describe the growth pattern of OFC gliomas. METHODS The study was performed on 10 brain specimens prepared according to Klingler's protocol and dissected using the fiber microdissection technique modified according to U.T., under the microscope at high magnification. RESULTS A detailed stratigraphy of the OFC was performed, from the cortex up to the frontal horn of the lateral ventricle. The interposed neural structures are described together with relevant neighboring topographic areas and nuclei. Combining anatomical and radiological data, it appears that the anatomical boundaries delimiting and guiding the macroscopical growth of OFC gliomas are as follows: the corpus callosum superiorly, the external capsule laterally, the basal forebrain and lentiform nucleus posteriorly, and the gyrus rectus medially. Thus, OFC gliomas seem to grow ventriculopetally, avoiding the laterally located neocortex. CONCLUSION The findings in our study supplement available anatomical knowledge of the OFC, providing reliable landmarks for a precise topographical diagnosis of OFC lesions and for perioperative orientation. The relationships between deep anatomic structures and glioma formations described in this study are relevant for surgery in this highly interconnected area.