The colonic microbiome is hypothesized to contribute to the induction and progression of colon cancer. While select bacterial species have been implicated in colon carcinogenesis, recent data also suggest that bacterial community organization and composition are carcinogenic. Studies of paired surgical CRC samples and normal colon mucosa as well as colon biopsies of healthy controls undergoing screening colonoscopy revealed that sporadic colon tumors located proximal to the hepatic flexure are characterized by invasive polymicrobial biofilms that extend to normal colon tissue far distant from the tumor. In contrast, colon mucosal biofilms occur much less frequently in individuals with colon cancer distal to the hepatic flexure and in only about 15% of mucosal samples from healthy colonoscopy controls. This talk will present an update on the intersection of individual microbes, biofilms and mechanisms of colon carcinogenesis. Together our studies support a model by which specific bacteria with their virulence genes as well as microbiota organization act with host immune responses to contribute to colon cancer pathogenesis.