Epperson MV, et al. - Experts understood that yolk sac tumors (YSTs) of the head and neck (H&N) are exceedingly rare and typically carry a poor prognosis and recognized the likelihood of heightened incidence in individuals with Aicardi Syndrome and the ramifications this has on early diagnosis and treatment in this population. On the contrary, the poor prognosis formerly defined, both individuals with Aicardi syndrome had an outstanding chemotherapeutic response showed via normalization of alpha-fetoprotein levels and imaging. Rare germ cell tumors of the H&N, like YSTs, have now been recorded in various individuals with Aicardi syndrome, suggesting a potential relationship provided the rarity of these tumors in the population. In these individuals, YSTs should be acknowledged in the differential diagnosis of H&N masses, with stress on early tissue diagnosis and treatment.