Cancer heterogeneity refers to the presence of distinct genetic and phenotypic subpopulations within a tumor, which can affect treatment outcomes and biomarker discovery. Advances in genomic techniques have revealed that tumors may contain multiple subclones with different genetic alterations, a phenomenon known as intra-tumor heterogeneity. This heterogeneity can influence clinical outcomes and is increasingly recognized in the context of targeted therapies. Understanding the mechanisms that drive intra-tumor heterogeneity, including both iatrogenic and tumor-specific factors, is crucial for improving cancer treatment. The review discusses the evidence supporting the extent, causes, and consequences of intra-tumor heterogeneity, and how this knowledge can be integrated into future clinical practice and research to optimize patient care. Intra-tumor heterogeneity is characterized by the presence of subpopulations with distinct genotypes and phenotypes, which may exhibit different biological behaviors. The advent of deep sequencing techniques has increased awareness of intra- and inter-tumor heterogeneity. While some features of intra-tumor heterogeneity are part of routine pathology, its role in clinical decision-making remains limited. The review highlights the impact of genetic intra-tumor heterogeneity on treatment stratification and therapeutic outcomes. Clonal evolution models suggest that genetic instability contributes to tumor heterogeneity, with driver and passenger mutations playing key roles. The CSC hypothesis may also explain intra-tumor heterogeneity. Tumor heterogeneity is a dynamic state that allows tumors to adapt to changing microenvironments. Studies have shown that intra-tumor heterogeneity can lead to differential responses to therapy and may complicate the identification of predictive biomarkers. Next-generation sequencing technologies are providing new insights into the genetic diversity within and between tumors. Evidence from studies in breast cancer and other solid tumors supports the presence of intra-tumor heterogeneity. The review also discusses the implications of tumor heterogeneity for targeted therapies, including drug resistance and the need for more effective biomarkers. The review emphasizes the importance of understanding tumor heterogeneity for improving cancer treatment. It highlights the challenges posed by tumor heterogeneity, including the need for more comprehensive tissue sampling and the potential for drug resistance. The review concludes that future research should focus on longitudinal studies of tumor evolution and the development of new technologies to better understand and manage tumor heterogeneity. The integration of this knowledge into clinical practice is essential for improving patient outcomes.Cancer heterogeneity refers to the presence of distinct genetic and phenotypic subpopulations within a tumor, which can affect treatment outcomes and biomarker discovery. Advances in genomic techniques have revealed that tumors may contain multiple subclones with different genetic alterations, a phenomenon known as intra-tumor heterogeneity. This heterogeneity can influence clinical outcomes and is increasingly recognized in the context of targeted therapies. Understanding the mechanisms that drive intra-tumor heterogeneity, including both iatrogenic and tumor-specific factors, is crucial for improving cancer treatment. The review discusses the evidence supporting the extent, causes, and consequences of intra-tumor heterogeneity, and how this knowledge can be integrated into future clinical practice and research to optimize patient care. Intra-tumor heterogeneity is characterized by the presence of subpopulations with distinct genotypes and phenotypes, which may exhibit different biological behaviors. The advent of deep sequencing techniques has increased awareness of intra- and inter-tumor heterogeneity. While some features of intra-tumor heterogeneity are part of routine pathology, its role in clinical decision-making remains limited. The review highlights the impact of genetic intra-tumor heterogeneity on treatment stratification and therapeutic outcomes. Clonal evolution models suggest that genetic instability contributes to tumor heterogeneity, with driver and passenger mutations playing key roles. The CSC hypothesis may also explain intra-tumor heterogeneity. Tumor heterogeneity is a dynamic state that allows tumors to adapt to changing microenvironments. Studies have shown that intra-tumor heterogeneity can lead to differential responses to therapy and may complicate the identification of predictive biomarkers. Next-generation sequencing technologies are providing new insights into the genetic diversity within and between tumors. Evidence from studies in breast cancer and other solid tumors supports the presence of intra-tumor heterogeneity. The review also discusses the implications of tumor heterogeneity for targeted therapies, including drug resistance and the need for more effective biomarkers. The review emphasizes the importance of understanding tumor heterogeneity for improving cancer treatment. It highlights the challenges posed by tumor heterogeneity, including the need for more comprehensive tissue sampling and the potential for drug resistance. The review concludes that future research should focus on longitudinal studies of tumor evolution and the development of new technologies to better understand and manage tumor heterogeneity. The integration of this knowledge into clinical practice is essential for improving patient outcomes.