The advent of high-throughput sequencing has revealed that our genome is pervasively transcribed into both coding and non-coding RNAs (ncRNAs), challenging the traditional definition of "gene." This review highlights the blurred dichotomy between coding and non-coding RNAs, emphasizing that many genes produce both types of transcripts. The authors discuss the implications of this dual functionality in gene expression and biological outcomes, particularly in cancer. They also address methodological challenges in studying bifunctional genes and explore the therapeutic potential of these intricate mechanisms in anticancer therapies. The review covers various examples of bifunctional genomic loci, including those that express both mRNAs and ncRNAs through alternative splicing, back-splicing, and antisense transcription. Additionally, it examines how mRNA 5'UTRs, CDS, and 3'UTRs can exert non-coding functions, and how ncRNAs can carry ORFs translated into peptides. The authors conclude by discussing the therapeutic opportunities and challenges associated with bifunctional genes in cancer research.The advent of high-throughput sequencing has revealed that our genome is pervasively transcribed into both coding and non-coding RNAs (ncRNAs), challenging the traditional definition of "gene." This review highlights the blurred dichotomy between coding and non-coding RNAs, emphasizing that many genes produce both types of transcripts. The authors discuss the implications of this dual functionality in gene expression and biological outcomes, particularly in cancer. They also address methodological challenges in studying bifunctional genes and explore the therapeutic potential of these intricate mechanisms in anticancer therapies. The review covers various examples of bifunctional genomic loci, including those that express both mRNAs and ncRNAs through alternative splicing, back-splicing, and antisense transcription. Additionally, it examines how mRNA 5'UTRs, CDS, and 3'UTRs can exert non-coding functions, and how ncRNAs can carry ORFs translated into peptides. The authors conclude by discussing the therapeutic opportunities and challenges associated with bifunctional genes in cancer research.