Lymphocytosis associated with viral infection is generally polyclonal or oligoclonal. In this article, we describe a case of transient monoclonal CD8+/CD57+ T-cell lymphocytosis with large granular lymphocyte (LGL) morphology occurring after primary CMV infection and review cases of virus-associated monoclonal CD8+ T-cell expansions reported in the literature. Several clinical features shared by virus-associated monoclonal CD8+ T-cell expansions suggest the reactive nature of the lymphocytosis. Based on this, our case report and those reported in the literature support the notion that T-cell receptor clonality per se is not necessarily indicative of malignancy. These observations further corroborate the need for a close follow-up before assigning the diagnosis of LGL leukemia to individuals developing monoclonal CD8+ T-cell expansions.