Latent Epstein-Bar virus genomes undergo epigenetic modifi cations which are dependent on the respective tissue type and cellular phenotype. These defi ne distinct viral epigenotypes corresponding with latent viral gene expression profi les. Viral Latent Membrane Proteins 1 and 2A can induce cellular DNA methyltransferases, thereby infl uencing the methylation status of the viral and cellular genomes. Therefore, not only the viral genomes carry epigenetic modifi cations, but also the cellular genomes adopt major epigenetic alterations upon EBV infection. The distinct cellular epigenotypes of EBV-infected cells differ from the epigenotypes of their normal counterparts. In Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBVaGC) signify cant changes in the host cell methylome with a strong tendency towards CpG island hypermethylation are observed. Hypermethylated genes unique for EBVaGC suggest the existence of an EBV-specifi c “epigenetic signature”. Contrary to the primary malignancies carrying latent EBV genomes, lymphoblastoid cells (LCs) established by EBV infection of peripheral B cells in vitro are characterized by a massive genome-wide demethylation and a signifi cant decrease and redistribution of heterochromatic histone marks. Establishing complete epigenomes of the diverse EBV-associated malignancies shall clarify their similarities and differences and further clarify the contribution of EBV to the pathogenesis, especially for the epithelial malignancies, NPC and EBVaGC.