Topographical orientation relies on several cognitive strategies adopted by humans to move within the environment. In the present study, we investigate whether mental representation disorders affect specific cognitive mechanisms subserving human orientation. In order to differentiate distinct cognitive mechanisms involved in topographical orientation, we created a human version of the well-known "Morris Water Maze" and tested left and right brain damaged patients in a place-learning task. The test required the subjects to explore an experimental room in which no visual cues were present, find a target location, and then reach it in different conditions. The ability to memorize target locations in short- and long-term memory was also assessed. We found that all participants were able to reach the target location by using idiothetic cues (vestibular inputs, motor efferent copy, etc.). On the other hand, when starting position changed and re-orientation was necessary to reach the target location, in order to compute a new trajectory, only patients affected by representational neglect got lost. These results provide the first neuropsychological evidence of involvement of mental representation in a specific cognitive process allowing humans to reach a target place from any location in the environment.