To the multiple factors that may eventually result in colorectal cancer (CRC), strains of E. coli have now been added, in particular strains producing colibactin from their polyketide synthesis (pks) locus. The evidence and mechanistic explanations for this unfortunate effect of what is in most cases a harmless commensal are discussed in the first part of this review. In the second part, observations are presented and discussed that do not fit with the hypothesis that colibactin-producing E. coli produce CRC. The last part of this review is reserved for an alternative explanation of the function of this enigmatic colibactin, a toxin that has not yet been isolated. It is hypothesized that E. coli preferentially colonizes cancerous lesions as an effect rather than a cause and that colibactin production provides a selective advantage to compete with other bacteria.