Increasing evidence indicates a key role for the bacterial microbiota in carcinogenesis. In fact, as much as 20% of the global cancer burden has been estimated to be caused by microbial agents. Many researchers believe the potential mechanism is through resident microbes’ influence on the immune system, with their abilities to dial up or dampen inflammation, as well as to manipulate the capabilities of various immune cells. Based on data from studies using gnotobiotic mouse models colonized with one or more specific bacteria, it appears that microbiota can alter cancer susceptibility and progression by diverse mechanisms, such as modulating inflammation, inducing DNA damage, and producing metabolites involved in oncogenesis or tumor suppression. Emerging evidence suggests that microbiota can be manipulated for improving cancer treatment. However, nothing has been published on the possibility of using tissue microbiome population analyses in patient samples to diagnose, monitor, or treat cancer.