N⁶-Methyladenosine (m⁶A), the most prevalent internal modification in eukaryotic mRNA, has been extensively and increasingly studied over the past decade. Dysregulation of RNA m⁶A modification and its associated machinery, including writers, erasers and readers, is frequently observed in various cancer types, and the dysregulation profiles might serve as diagnostic, prognostic and/or predictive biomarkers. Dysregulated m⁶A modifiers have been shown to function as oncoproteins or tumour suppressors with essential roles in cancer initiation, progression, metastasis, metabolism, therapy resistance and immune evasion as well as in cancer stem cell self-renewal and the tumour microenvironment, highlighting the therapeutic potential of targeting the dysregulated m⁶A machinery for cancer treatment. In this Review, we discuss the mechanisms by which m⁶A modifiers determine the fate of target RNAs and thereby influence protein expression, molecular pathways and cell phenotypes. We also describe the state-of-the-art methodologies for mapping global m⁶A epitranscriptomes in cancer. We further summarize discoveries regarding the dysregulation of m⁶A modifiers and modifications in cancer, their pathological roles, and the underlying molecular mechanisms. Finally, we discuss m⁶A-related prognostic and predictive molecular biomarkers in cancer as well as the development of small-molecule inhibitors targeting oncogenic m⁶A modifiers and their activity in preclinical models.