Background: Since subjects with Rett syndrome (RTT) focus their attention mainly on the faces of people with whom they interact, in this study the role of a human-like avatar in enhancing cognitive processes was examined. More in depth, this study examined subjects with RTT performing attention and memory tasks with and without a virtual avatar.Method: Thirty-six girls with RTT participated in the study. They were matched for mental age and randomly submitted to two conditions (with and without virtual avatar) with two tasks (over-selectivity and memory paradigms). Results: The results indicated that the RTT group exposed to the virtual avatar condition, presented better attention and memory abilities than the matched RTT group without the avatar condition. Discussion: The results were discussed in light of the relationship between motivation, attention and memory in RTT.