Kaposi sarcoma is considered a neoplasm of lymphatic endothelium infected with Kaposi sarcoma–associated herpesvirus. It is characterized by the expression of lymphatic lineage–specific genes by Kaposi sarcoma tumor cells. Here we show that infection of differentiated blood vascular endothelial cells with Kaposi sarcoma–associated herpesvirus leads to their lymphatic reprogramming; induction of ∼70% of the main lymphatic lineage–specific genes, including PROX1, a master regulator of lymphatic development; and downregulation of blood vascular genes.