By reviewing the syndromic manifestation, transsexualism in characterized as a psychiatric entity, apart from homossexualism and transvestism. The two main feasible etiologic causes of transsexualism are discussed: the psychoanalytical hypothesis based upon psycossexual regression with imprinting of maternal figure and the neuroendocrine model which assumes alterations of the gender role identity centers in the hypothalamus. On the grounds of the latter explanation and after the scheme that seems to occur in the Morris syndrome whose cells (XY) do not respond to the masculinizing effect of plasma testosterone, it is proposed that transsexuals should possess detectable or cryptic sex-chromosome mosaicism affecting hypothalamic centers of gender role identity which do not respond to the androgenic secretion produced by primitive gonad. This possibility explains the excessive prevalence of the syndrome among men, its typical features in the male as well as its sporadic occurrence. Cytogenetic investigation reveals that the frequency (32%) of sex-chromosome mosaicism among 25 transsexuals and 40 normal control people, both groups presenting the proportion of the mosaicism practically null. The karyotypic criterion as a valuable aid in the syndrome diagnosis is considered.