Abstract Objective: Transgender youth face enormous barriers to accessing medically necessary gender-transition-related care, including neuropsychological evaluation. Normative data for cognitive and psychological measures have not been developed for transgender individuals, creating a dilemma for neuropsychologists. Sex-based differences in certain domains and literature identifying brain-based changes with hormone therapy are additional factors. The aim of this study is to discuss unique considerations when evaluating medically complex transgender individuals. Method: A 14-year-old transgender male (assigned female at birth) with a history of acute lymphoblastic leukemia treated with chemotherapy, presented for evaluation to assess late effects of treatment and psychiatric complexities. He experienced gender dysphoria since childhood, identified as non-binary during early adolescence, and recently identified as male. He had not yet begun medical treatment (puberty blockers, hormone therapy) related to gender-affirming care. Results: Thoughtful consideration informed by current literature was made regarding test selection, norm usage, and data interpretation. Gender combined norms were used when available. Norms based on preferred or birth-assigned gender were used within the context of known sex-based differences in certain domains and low likelihood of brain-based changes at this time. Results revealed average or better performance across most domains, mild weakness in visual-motor integration and motor-dependent processing speed, and anxiety. Conclusion: Outcomes were believed related to chemotherapeutic late effects along with complex psychosocial factors. This case highlights the need for a thoughtful approach to the neuropsychological evaluation of transgender youth from test and norm selection to data interpretation along with consideration of unique psychosocial factors which are likely to be present for transgender individuals.