Interphase chromosomes form distinct spatial domains called chromosome territories (CTs). The arrangement of CTs is non-random and correlated with cellular processes such as differentiation. The purpose of this study is to provide some behavior information of CTs during lymphocyte EBV-infection, which is thought to be a general extra-biological model. Three-dimensional fluorescence in situ hybridization (3D-FISH) was performed on human lymphocytes every 24 h over 96 h periods in EBV-infection. Chromosomes 17 and 18 were selected as target territories for similar size and different gene density. The data indicate that the radial position of territories 17 was altered with time, whereas territories 18 showed relative stable localization. The relative CT volume of CTs 18 to 17 also changed with infection. Our study is the first to examine the timely changes of chromatin positioning and folding in EBV-lymphocyte infection. Dynamic changes in position and folding status of target chromosomes reflected an impact of EBV infection on genome stability.