The past decade has seen significant advancements in understanding the role of epigenetic processes in cancer, from both a biological and translational perspective. Next-generation sequencing has revolutionized the visualization of the human epigenome, revealing surprising links between epigenetic abnormalities and genetic mutations. These abnormalities are leading to the development of specific markers for cancer detection, diagnosis, and prognosis. The enzymatic processes that control the epigenome offer new therapeutic opportunities to reverse transcriptional abnormalities inherent in cancer. Key advances include the understanding of chromatin architecture and gene expression states, the role of DNA methylation in cancer, and the importance of epigenetic changes in cancer initiation and progression. Abnormal gains and losses of DNA methylation, particularly in promoter CpG islands, are common in various cancers and contribute to gene silencing. The balance between transcriptionally permissive and repressive chromatin modifications maintains genome-wide gene expression states, and the bivalent state of key developmental genes in embryonic stem cells is crucial for regulatory flexibility. Recent findings also highlight the importance of epigenetic changes in cancer, such as the abnormal retention of Polycomb group (PcG) complexes and the loss of DNA methylation. These changes can lead to the expansion of stem and progenitor cells, increasing the risk of cancer. Additionally, the inheritance of certain genetic alterations can increase the probability of *de novo* methylation of key genes, contributing to familial cancers. Translational advances include the development of DNA methylation biomarkers for cancer risk assessment, early detection, and prognosis. For example, hypermethylation of genes like *CDKN2A* and *CDH13* in colon cancer and *GSTP1* in prostate cancer can predict risk and response to therapy. Epigenetic therapies, such as DNA methyltransferase inhibitors and histone deacetylase (HDAC) inhibitors, are showing promise in clinical trials, with recent FDA approvals for treating myelodysplastic syndrome and cutaneous T cell lymphoma. The future holds exciting prospects for translating these findings into new prevention and therapeutic strategies, including the development of epigenetic therapies and the targeting of specific epigenetic alterations. The field is rapidly evolving, and the next decade will see further progress in defining the cancer epigenome and developing effective treatments.The past decade has seen significant advancements in understanding the role of epigenetic processes in cancer, from both a biological and translational perspective. Next-generation sequencing has revolutionized the visualization of the human epigenome, revealing surprising links between epigenetic abnormalities and genetic mutations. These abnormalities are leading to the development of specific markers for cancer detection, diagnosis, and prognosis. The enzymatic processes that control the epigenome offer new therapeutic opportunities to reverse transcriptional abnormalities inherent in cancer. Key advances include the understanding of chromatin architecture and gene expression states, the role of DNA methylation in cancer, and the importance of epigenetic changes in cancer initiation and progression. Abnormal gains and losses of DNA methylation, particularly in promoter CpG islands, are common in various cancers and contribute to gene silencing. The balance between transcriptionally permissive and repressive chromatin modifications maintains genome-wide gene expression states, and the bivalent state of key developmental genes in embryonic stem cells is crucial for regulatory flexibility. Recent findings also highlight the importance of epigenetic changes in cancer, such as the abnormal retention of Polycomb group (PcG) complexes and the loss of DNA methylation. These changes can lead to the expansion of stem and progenitor cells, increasing the risk of cancer. Additionally, the inheritance of certain genetic alterations can increase the probability of *de novo* methylation of key genes, contributing to familial cancers. Translational advances include the development of DNA methylation biomarkers for cancer risk assessment, early detection, and prognosis. For example, hypermethylation of genes like *CDKN2A* and *CDH13* in colon cancer and *GSTP1* in prostate cancer can predict risk and response to therapy. Epigenetic therapies, such as DNA methyltransferase inhibitors and histone deacetylase (HDAC) inhibitors, are showing promise in clinical trials, with recent FDA approvals for treating myelodysplastic syndrome and cutaneous T cell lymphoma. The future holds exciting prospects for translating these findings into new prevention and therapeutic strategies, including the development of epigenetic therapies and the targeting of specific epigenetic alterations. The field is rapidly evolving, and the next decade will see further progress in defining the cancer epigenome and developing effective treatments.