Systemic Epstein-Barr virus-positive (EBV) T-cell lymphoma (TCL) of childhood is an uncommon TCL that occurs secondary to an acute or chronic EBV infection. The disorder is characterized by the monoclonal expansion of EBV T cells driven by an increased immune response and defect in regulatory pathways. Thus, systemic EBV TCL of childhood is frequently associated with a hyperinflammatory state, hemophagocytic lymphohistiocytosis (HLH) syndrome, and exhibits a fulminant clinical course with poor outcomes. Additionally, genetic alterations at specific chromosome loci, such as chromosome 22q11.2, are hypothesized to increase the chances of carcinogenic transformation and increase the risk of non-Hodgkin lymphoma later in life. Chemotherapy, immunotherapy, and allogenic stem cell transplants are treatment options with varying degrees of success. In this report, we describe a case of a 21-year-old male with a primary acute EBV infection that led to HLH syndrome. He was ultimately diagnosed with systemic EBV TCL of childhood. Despite treatment chemotherapy, the patient passed before an allogenic stem cell transplant could be performed. We explore the clinicopathological features of his disease and a possible new oncogenic locus at the t(1;22)(p22;q11.2) breakpoint. Our case underscores the importance of retaining a wide differential diagnosis, including unusual presentations of systemic EBV TCL of childhood, when presented with an adult case of HLH. It also highlights a possible new genetic locus associated with immunological malignancies that warrants further study.