Bacteria have been implicated in the initiation and progression of cancers originating on mucosal surfaces that either harbor a diverse microbial community (microbiota) or are routinely exposed to microbes from the environment (1–3). Far less is known about the potential for bacteria to influence tumors in body sites that are typically considered sterile. One hypothesis is that the abundant and diverse microbiotas found on mucosal surfaces may exert “remote control” by releasing small molecules into circulation (4, 5). An alternative, nonconflicting hypothesis is that the tumor microenvironment harbors microbes that exert local effects. This hypothesis is supported by the detection of bacteria in a growing number of tumor types (6, 7), although the reliability of distinguishing low-abundance bacteria from contamination has been questioned (8). On page 973 of this issue, Nejman et al. (9) present the most rigorous and comprehensive survey of bacteria in human tumor samples to date.
