The intestinal microbiome is associated with colorectal cancer. Although the mucosal microbiota better represents an individual’s local microbiome, studies on the colorectal cancer microbiota mainly reflect knowledge obtained from fecal samples. This systematic review aimed to summarize the current evidence on the relationship between the mucosal-associated bacterial microbiota and colorectal cancer. Searches were conducted in PubMed and Web of Science databases for publications comparing the mucosal microbiome of colorectal cancer patients with that of healthy controls, or with that of non-cancerous mucosal tissues. The primary outcomes were differences in microbial diversity and taxonomy. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Of the 5080 studies identified, 39 were eligible and included in the systematic review. No consistent results were identified for the α- and β-diversity, due to high heterogeneity in reporting and to differences in metrics and statistical approaches, limiting study comparability. Qualitative synthesis of microbial taxonomy identified 12 taxa with strong positive and 18 taxa with strong negative associations with colorectal cancer. Fusobacterium, Campylobacter, Parvimonas, Peptostreptococcus, Streptococcus, and Granulicatella were defined as enriched in colorectal cancer. Despite the methodological limitations of the studies, consistent evidence on bacterial taxa associated with colorectal cancer was identified. Prospective studies in large and well-characterized patient populations will be crucial to validate these findings.