Background: To date, research on spontaneous social interactions in mixed and non-mixed groups has not included exchanges with peer buddies. Object: In Study 1, socio-cognitive factors associated with the intention to volunteer to become a peer buddy for students with Autism Spectrum Disorder (ASD) were investigated. In Study 2, spontaneous social interactions in adolescents with ASD and a low level of support with selected peer buddies and with other students were compared. Method: In Study 1, social-cognitive abilities were investigated through the use of self-report questionnaires. Among typically developing students, their willingness to spontaneously volunteer to help a classmate with ASD was evaluated. Moreover, students were required to indicate among their classmates who were competent to volunteer and who were not. In Study 2, social interaction behaviors in mixed and non-mixed groups were observed and opportunely codified. Results: In Study 1, students expressing the intention to volunteer obtained higher scores on empathy scale and displayed more positive attitudes towards ASD than other classmates. Volunteers were, in turn, selected as peer buddies by their classmates. In Study 2, when students interacted with selected peer buddies engaged in the highest number of social positive interaction behaviors than they did in other kinds of groups. The worst social interactions were observed in non-mixed groups. Conclusions: Social behavior displayed by students with ASD appeared strongly influenced by social partners. Students with ASD seemed to more positively benefit from interactions with selected peer buddies compared to other mixed and non-mixed groups.