The use of circulating tumor DNA (ctDNA) in early breast cancer (BC) is gaining attention for its potential in screening, treatment evaluation, and minimal residual disease (MRD) detection. ctDNA analysis provides non-invasive, real-time tumor information, complementing tissue biopsies. However, its application in early BC has been limited due to lower ctDNA levels compared to metastatic BC. Advances in sequencing and bioinformatics, along with the use of methylome profiles, have increased interest in ctDNA analysis for early BC. This review discusses the analytical validity of current ctDNA tests and their clinical potential in early BC. ctDNA is released into the bloodstream through tumor cell death and is a fraction of cell-free DNA. It has a short half-life, making it a source of real-time tumor information. In metastatic BC, ctDNA analysis helps identify mutations predictive of treatment response. In early BC, ctDNA analysis is technically more challenging due to lower sensitivity, but advances in sequencing and bioinformatics are improving its application. Tumor-agnostic and tumor-informed approaches are used for ctDNA analysis. Tumor-agnostic methods do not require prior knowledge of tumor mutations, while tumor-informed methods require tumor sequencing and personalized assays. Both have advantages and limitations. Tumor-informed methods are generally more sensitive for detecting low variant allele frequencies but are more time-consuming. Analytical validity of ctDNA tests includes limit of detection, sensitivity, specificity, and robustness. Most current ctDNA assays have incomplete reporting of analytical validity, but development focuses on increasing sensitivity. Tumor-agnostic approaches include NGS panels, amplicon-based NGS, and hybridization capture NGS. Tumor-informed approaches include ddPCR and personalized amplicon-based NGS. Methylation analysis is important for identifying tissue-specific patterns and has been used in BC screening. Commercially available tests like Galleri™ and GuardantReveal™ have shown promise in detecting ctDNA. However, challenges remain in detecting early-stage BC due to low ctDNA levels. In clinical trials, ctDNA analysis has shown potential in monitoring MRD and guiding treatment decisions. However, challenges include false positives from clonal hematopoiesis and the need for further validation and standardization. The FDA is working on quality control projects to evaluate ctDNA tests. Comprehensive analytical validity assessments are essential for ctDNA to enter routine clinical practice. In early BC, ctDNA analysis is used for screening, treatment evaluation, and MRD monitoring. It has shown potential in detecting early-stage BC, but challenges remain in detecting early-stage disease. ctDNA analysis in urine and breast milk is also being studied for early BC detection. Future directions include improving sensitivity and specificity, expanding the use of fragmentomics, and validating ctDNA analysis in large clinical trials. The clinical utility of ctDNA in early BC is still under investigation, but it holds promise for personalized treatment and improved patient outcomes.The use of circulating tumor DNA (ctDNA) in early breast cancer (BC) is gaining attention for its potential in screening, treatment evaluation, and minimal residual disease (MRD) detection. ctDNA analysis provides non-invasive, real-time tumor information, complementing tissue biopsies. However, its application in early BC has been limited due to lower ctDNA levels compared to metastatic BC. Advances in sequencing and bioinformatics, along with the use of methylome profiles, have increased interest in ctDNA analysis for early BC. This review discusses the analytical validity of current ctDNA tests and their clinical potential in early BC. ctDNA is released into the bloodstream through tumor cell death and is a fraction of cell-free DNA. It has a short half-life, making it a source of real-time tumor information. In metastatic BC, ctDNA analysis helps identify mutations predictive of treatment response. In early BC, ctDNA analysis is technically more challenging due to lower sensitivity, but advances in sequencing and bioinformatics are improving its application. Tumor-agnostic and tumor-informed approaches are used for ctDNA analysis. Tumor-agnostic methods do not require prior knowledge of tumor mutations, while tumor-informed methods require tumor sequencing and personalized assays. Both have advantages and limitations. Tumor-informed methods are generally more sensitive for detecting low variant allele frequencies but are more time-consuming. Analytical validity of ctDNA tests includes limit of detection, sensitivity, specificity, and robustness. Most current ctDNA assays have incomplete reporting of analytical validity, but development focuses on increasing sensitivity. Tumor-agnostic approaches include NGS panels, amplicon-based NGS, and hybridization capture NGS. Tumor-informed approaches include ddPCR and personalized amplicon-based NGS. Methylation analysis is important for identifying tissue-specific patterns and has been used in BC screening. Commercially available tests like Galleri™ and GuardantReveal™ have shown promise in detecting ctDNA. However, challenges remain in detecting early-stage BC due to low ctDNA levels. In clinical trials, ctDNA analysis has shown potential in monitoring MRD and guiding treatment decisions. However, challenges include false positives from clonal hematopoiesis and the need for further validation and standardization. The FDA is working on quality control projects to evaluate ctDNA tests. Comprehensive analytical validity assessments are essential for ctDNA to enter routine clinical practice. In early BC, ctDNA analysis is used for screening, treatment evaluation, and MRD monitoring. It has shown potential in detecting early-stage BC, but challenges remain in detecting early-stage disease. ctDNA analysis in urine and breast milk is also being studied for early BC detection. Future directions include improving sensitivity and specificity, expanding the use of fragmentomics, and validating ctDNA analysis in large clinical trials. The clinical utility of ctDNA in early BC is still under investigation, but it holds promise for personalized treatment and improved patient outcomes.