Epstein-Barr virus and Cytomegalovirus have different oral manifestations which could be presented in the oral cavity most commonly as non-specific oral ulcerations and lymphadenopathy. A lot of people acquire primary infection with Cytomegalovirus and if they later become immunosuppressed, such as human immunodeficiency virus (HIV), Cytomegalovirus is likely to become reactivated. We present a clinical case of a young man with multiple painful oral ulcerations with duration more than several years. The patient applied different types of local creams without significant results. After the clinical examination our recommendation was to investigate serum levels of EBV-IgG and CRP-IgG and HIV-1 and-2, complete blood count with differential (CBC), folic acid, CRP. The laboratory results revealed positive IgG antibodies against CMV and EBV, folic acid deficiency.