| Summary: | Background: Iatrogenic cerebrospinal fluid leak (iCSF-L) is a major complication of endonasal surgeries whose occurrence is always a potential adverse event due to anatomical variation/asymmetry of the skull base (SB). The aim of this manuscript is to provide a topographical map of iCSF-L and to investigate the role of SB asymmetry in iCSF-L occurrence. Methods: In this retrospective study, the location of iCSF-L dural defect was studied and compared to patients affected by spontaneous and post-traumatic CSF-L. Considering only iCSF-L, after having collected the SB asymmetry data, the Keros, Gera, distance of the anterior ethmoidal artery from the SB, frontal sinus pneumatization, and Thailand–Malaysia–Singapore score classifications were compared to a control group of patients. Results: A total of 153 CSF-Ls (103 spontaneous, 37 iatrogenic, and 13 traumatic) were included. A significant association was noted (<i>p</i> < 0.001) between the nature of the CSF-L and the areas involved. Considering iCSF-Ls, only the Gera classification was significantly different (<i>p</i> < 0.05) and the most reliable in predicting the risk of dural transgression (AUC = 0.719). Conclusions: ICSF-Ls present peculiar regional SB involvement with the cribriform plate, with the ethmoidal roof being the most involved. After having assessed the asymmetry of the SB, the Gera classification was the most reliable one.
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