Harlequin syndrome (HS) is a rare disorder of the autonomic nervous system, caused by unilateral damage to sympathetic fibers innervating the face. The symptoms appear in response to physical activity or heat exposure and present with hemifacial flushing and asymmetric sweating. HS can be idiopathic or associated with an underlying disease. One of the causes of HS in the pediatric population might be a differentiated benign neuroblastic neoplasm-ganglioneuroma. It is often detected in older children and adults, with the most typical location within the posterior mediastinum. In this paper, we present the case of a 3-year-old patient with face discoloration and a massive mediastinal tumor (ganglioneuroma). This study highlights the importance of identifying the cause of HS and the possibility of ganglioneuroma occurring in younger children.