HCMV can infect a wide range of cell types that may be present within the tumor microenvironment, such as monocyte/macrophages, fibroblasts, epithelial and endothelial cells. While several studies have found evidence for direct infection of tumor cells via IHC staining [10, 11], detection of viral DNA by PCR from fixed tissue samples precludes direct identification of the cell type harboring the virus. It may be that the cell type infected varies from case to case, just like the combination of specific mutations that lead to tumor initiation in a given individual. We favor the notion that immune cells harboring latent HCMV infiltrate the tumor, because monocytes are a well-documented reservoir for HCMV [74–76] and this scenario could lead to significant variability from tumor to tumor depending on the number of infected infiltrating cells and whether they reactivate virus that goes on to infect other cells in the tumor microenvironment. Transcriptional analysis of HCMV-infected monocytes revealed a unique M1/M2 polarization signature that included induction of both M1 type inflammatory cytokines like IL-1, IL-6, and TNFα, as well as upregulation of M2 type cytokines like IL-10 and IL-18 . The presence of these conflicting signals in the tumor environment has been associated with neoplastic progression, suggesting that HCMV could tip the balance in favor of this process .