A hypothesis for EBV-induced lymphomagenesis. EBV transforms B lymphocytes, providing cells with much potentially oncogenic information. However, the viral genes these EBV-positive “proto” tumor cells express are immunogenic, placing the cells under strong negative selection by the immune system. In response, tumor cells evolve to express fewer viral genes by gaining cellular mutations that replace the functions of viral oncogenes. Different tumor cells express distinct sets of latent viral genes reflecting their in vivo evolution away from dependence on the virus and toward dependence on cellular mutations. The lengths of the lines for each tumor cell line reflect the hypothesized extent of this evolution. See the complete figure in the article beginning on page 1977.