Objectives:The purpose of this systematic review is to examine the different variations of the median nerve (MN) and the diagnostic methods used to identify carpal tunnel syndrome (CTS), a common neuropathy resulting from the entrapment of the MN within the carpal tunnel. Understanding the different variations of the MN is crucial in order to prevent injuries during surgical treatment of the syndrome. Materials and methods:Data were extracted from studies published in PubMed. A detailed search in PubMed was performed for studies that reviewed the variations of the MN and CTS. Results:There are two main classifications of the MN, known as the Lanz and Amadio categories. Lanz's classification is the one being mostly used in the surgical literature, with group 3 (Bifid MN) being the main cause of the CTS. Additionally, there are branches and anastomosis of the MN that do not fit into either category, with the third common digital branch being the most injured nerve during carpal tunnel release surgery. Diagnostic techniques for CTS include physical examination combined with NCS tests, magnetic resonance imaging (MRI), ultrasound, or elastography. While NCS has been previously the most commonly used diagnostic method, the recent literature suggests that ultrasound and elastography are the most accurate techniques. Conclusions:In order to minimize injuries during carpal tunnel release surgery, it is crucial to have knowledge on the different variations of the MN that cause CTS. Additionally, this review emphasizes the significance of the current diagnostic methods, which not only make CTS more affordable but also facilitate easier recognition of the condition.