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Recurrent cerebrospinal fluid (CSF) rhinorrhea caused by sequential, anatomically separated skull base defects is rarely reported in the literature. Neither management nor etiology has been sufficiently investigated. We present an illustrative case and a systematic review of the literature regarding etiology, diagnostics, and management of this rare phenomenon. A systematic literature search looking for articles reporting sequential CSF leaks with multiple skull base defects was performed. Data from included articles were descriptively reported, and the quality of the included studies was assessed with Grading of Recommendations Assessment, Development and Evaluation. A 71-year-old woman with posttraumatic CSF rhinorrhea and left-sided CSF otorrhea due to a left-sided horizontal fracture of the petrous bone presented at our institution. After initial surgical repair and a 10-week symptom-free interval, CSF rhinorrhea recurred. Imaging revealed a preexisting contralateral meningoencephalocele of the lateral sphenoid recess causing recurrent CSF rhinorrhea most likely after initial traumatic laceration. The defect was successfully treated. A literature search identified 366 reports, 6 of which were included in the systematic review with a total of 10 cases. Quality was deemed good in 8 of 10 cases. The most common location for primary and sequential CSF leaks was along the sphenoid bone (4/10 and 5/10 patients, respectively). All publications except one reported the presence of a meningo (encephalo)cele as cause of the sequential CSF leak. Occurrence of recurrent CSF rhinorrhea due to an anatomically separated sequential skull base lesion remains a rare phenomenon. Reassessment of imaging studies and a structured diagnostic workup to detect sequential CSF leaks independent of the primary lesion should is recommended. [ABSTRACT FROM AUTHOR]