Gender dysphoria (GD) (DSM-5) or transsexualism (ICD-10) refers to the marked incongruity between the experience of one’s gender and the sex at birth. In this case report, we describe the use of LSD as a triggering factor of confusion in the gender identity of a 39-year-old male patient, with symptoms of psychosis and 25 years of substance abuse, who sought psychiatric care with the desire to undergo sex reassignment surgery. The symptoms of GD/psychosis were resolved by two therapeutic measures: withdrawal of psychoactive substances and use of a low-dose antipsychotic. We discuss the hypothesis that the superior parietal cortical area may be an important locus for body image and that symptoms of GD may be related to variations underlying this brain region. Finally, this case report shows that some presentations of GD can be created by life experience in individuals who have underlying mental or, synonymously, neurophysiological abnormalities.