Lymphomatous involvement of the larynx is a rare entity. We present a case of atypical laryngotracheitis as the initial manifestation of non-Hodgkin’s lymphoma in a pediatric patient. The diagnosis was aided through the use of microbial cell-free DNA (mcfDNA) testing, which detected the presence of Epstein-Barr virus in the patient’s plasma. This enabled the consideration of an Epstein-Barr virus–related lymphoproliferative process, leading to additional workup and the final diagnosis of lymphoma. To our knowledge, this is the first case of mcfDNA testing leading not simply to an infectious organism, but further to a new oncologic diagnosis. Plasma mcfDNA testing has the potential to inform clinical practice beyond classic infectious disease manifestations. In this article, we review both the possible future applications and the areas of further investigation that remain.