Most cases of infectious mononucleosis (IM) are caused by Epstein-Barr virus (EBV). Other pathogens have been reported to cause heterophile-negative mononucleosis-like syndrome, including cytomegalovirus (CMV) and human immunodeficiency virus type-1 (HIV-1). Primary CMV infection is often asymptomatic in immunocompetent individuals. In this article, we describe a patient with prolonged fever and fatigue, who developed transient monoclonal CD8+ T-cell lymphocytosis after primary CMV infection. Monoclonal gene rearrangement of T-cell receptor (TCR) beta locus was transiently detected in DNA from peripheral lymphocytes. Monoclonal rearrangement and atypical lymphocytosis disappeared after treatment with anti-viral agents. These observations imply that monoclonal expansion of T-cells could be a reactive phenomenon of primary CMV infection and TCR gene rearrangement is not specific for malignancy. Physicians should carefully follow patients with monoclonal expansion of CD8+ T-cells after CMV-IM in order to rule out T cell malignancy.