Trans women (TW) have a high prevalence of poor mental health. Gender-affirming treatments could reduce distress regarding their gender incongruity. However, psychiatric comorbidities might complicate the management or even confirmation of being transgender. We reported three TW with complex mental illnesses, including anxiety disorder with cultural explanation, neurodevelopmental disorders with cross-dressing, and severe personality disorder accompanied by major depression. All cases received both psychiatric and gender-affirming treatments, which demonstrated promising outcomes. Along with gender dysphoria (GD), psychiatric comorbidities also altered these TW's identity and manifestations. Recognition of such conditions would be beneficial in providing care for all TW, both with and without GD.