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Microbial biofilms are extremely organized groups of microorganisms entrenched in an extracellular polymeric substance (EPS) network which facilitates persistence, shielding against host immunity, and resistance to antimicrobial activity. Although traditionally related to chronic infections and complications in devices, recent evidence suggests that biofilms are also important in cancer formation and progression. Recent research has shown that microbial communities can be present in tumor micro-environment, and biofilms can be actively involved in carcinogenesis as opposed to being passive colonizers. In this chapter, a new association between biofilms and cancer is discussed through an understanding of their existence in various malignancies such as colorectal, oral, pancreatic, breast, gastric, lung, cervical, and liver cancers. The mechanisms of biofilms and tumor development are in detail discussed such as chronic inflammation, generation of genotoxic metabolites, immune modulation and destabilization of epithelial barriers. These mechanisms induce genomic instability, damage DNA, immunomodulation and the activation of oncogenic signaling pathways that promote the initiation and progression of tumors. Moreover, the chapter suggests the effect of biofilms on the tumor microenvironment, angiogenesis, metastasis, and cancer therapy resistance to chemotherapy, radiotherapy, and immunotherapy. Clinical implications are also discussed, and the problem includes difficulties in diagnosing, prognostic implications, and the effect of biofilm-related infections on patient outcomes. Although mounting evidence is obtained, the role of biofilms in oncology is under-recognized since it is challenging to detect, might be mistaken as contamination, and there is a lack of awareness in cancer research. The knowledge of the intricate relationships that exist between microbial biofilms and host tissues can provide fresh prospects to better diagnostics, specific antimicrobial therapy, and new treatment methods in cancers.