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Transsexualism is when an individual identifies with a gender inconsistent or not culturally associated with their assigned sex, i.e. in which a person's assigned sex at birth conflicts with their psychological gender. A medical diagnosis can be made if a person experiences discomfort as a result of a desire to be a member of the opposite gender, or if a person experiences impaired functioning or distress as a result of that gender identification.

Transsexualism is stigmatized in many parts of the world but has become more widely known in Western culture in the mid to late 20th century, concurrently with the sexual revolution and the development of sex reassignment surgery (SRS). Violence, discrimination, or negative attitudes towards transsexualism often accompany certain religious beliefs or cultural values. In popular culture, transsexualism is often incorrectly conflated with drag performance and cross-dressing.

There are cultures that have no difficulty integrating people who change gender roles, often holding them with high regard. Some maintain that transsexuals uphold the traditional role for "Two-Spirit" people found among certain Native American tribes.