Approximately 18% of human cancers have a viral etiology and the majority of these involve transformation of epithelial cells. Viral proteins transform epithelia by inducing alterations in the normal cell growth and differentiation pathways through the targeting of host proteins. Among the DNA viruses responsible for causing carcinomas are the human papillomaviruses as well as several members of the herpes and polyomavirus families. A number of techniques have been developed to study the mechanisms by which viruses immortalize epithelial cells and alter differentiation properties. These methods include the generation of immortalized lines by transfection or infection as well as the use of organotypic raft cultures, suspension in methylcellulose, and treatment with high calcium levels to examine how differentiation is altered.