Sexual orientation is a complex area. It is unclear to date how people precisely establish their preferred sexual objects. This paper presents two cases, whose heterosexual preference were changed in late adolescent age after a severe psychological event, to draw attention to the study of the possible underlying mechanism. Case 1, one identical male twin, was seriously punished at age 12 years, as he loved a girl in his classroom. Afterwards, he feared to contact with girls, and became attracted to young men at age 17 years, and kept same-sex sexual behaviors since then. However, his twin brother is always heterosexual. Case 2, a girl at age 16 years, was unexpectedly betrayed by her boyfriend, she bore great pain and distress in the beginning. Since then, she had a definite opinion that men were unbelievable, and gradually turned her heterosexual preference and had same-sex sexual behaviors with a girl classmate more than 3 years. Our case presentation indicates that severe frustration of primary heterosexual desires or behaviors and the successive cognitive regulation might lead susceptible adolescents into reorienting their sexual preference. The role of prefrontal cortex and related neuromodulatory pathways were discussed.