Purpose: Injury to the third common digital nerve (TCDN) has been described as the most commonly injured digital nerve with carpal tunnel release. Anatomic variations in the origin and course of the third common digital nerve from the median nerve may place this structure at risk. Anatomic landmarks may be useful to predict the location of this third common digital nerve to minimize the risk for injury to this structure with carpal tunnel release. Methods: 17 cadaver hands were used to determine the origin and course of the TCDN. The origin of the TCDN from the median nerve was identified in relation to the transverse carpal ligament, cardinal line, and superficial palmer arch. The course of the TCDN was inspected in relation to the scaphoid tubercle and ring finger. Results: Three anatomic variations for the origin of the TCDN were identified: Type 1 originating proximal to distal edge of transverse carpal ligament (1/17), Type 2 distal to the transverse carpal ligament but proximal to superficial palmer arch (13/17), Type 3 at or distal to superficial palmer arch (3/17). The origin of the TCDN was measured an average 5mm +/-1.2 mm distal to the cardinal line. The TCDN coursed along an oblique vector from the scaphoid tubercle to the mid-point of the palmer digital crease of the ring finger for Type 2 and Type 3. The oblique course of the TCDN passes across the longitudinal vector used for carpal tunnel release near the cardinal line. Distal to the cardinal line the TCDN passed under the superficial palmer arch in all 17 dissections. Conclusion: The anatomic landmarks of the center of the middle finger and cardinal line and scaphoid tubercle to mid point of palmer digital crease of ring finger can be used to predict the origin and course of the TCDN, although a Type 1 origin of the TCDN may increase the risk of injury with carpal tunnel release.