This study is the first contribution to the understanding of gender differences in best friendship patterns of adolescents sexual minorities. We explored friendship patterns, self-disclosure, and internalized sexual stigma in an Italian sample of lesbian (N = 202) and gay (N = 201) adolescents (aged 14-22 years). We found gender differences in cross-sex and cross-orientation patterns of best friendship. Gay men (52%) reported more cross-sex friendships than lesbians (20%). The 52% of participants had cross-orientation friendships, and no differences were found between lesbians and gay men. Lesbian and gay men with a cross-orientation best friend showed a lower level of internalized sexual stigma. Gay men with cross-orientation friendship showed a low level of internalized sexual stigma and less conflict with a best friend. For gay men and lesbian participants, self-disclosure to the best friend was better predicted by internalized sexual stigma and self-disclosure. Future studies may provide direct comparisons between heterosexual and sexual minority individuals. (Contains 2 tables.)