<p>Circulating tumor DNA has emerged as a minimally invasive and dynamic tool for providing real-time genetic insights into solid tumors, including breast cancer. Circulating tumor DNA is released into the bloodstream through apoptosis, necrosis, or active secretion, and it reflects tumor heterogeneity, which continues to be a major challenge in breast cancer treatment. Advances in high-sensitivity technologies, such as next-generation sequencing and digital polymerase chain reaction, have enabled the detection of key genetic alterations, offering applications in early diagnosis, monitoring minimal residual disease, identifying drug resistance mechanisms, and predicting relapse. Some circulating tumor DNA-based tests have already received regulatory approval for clinical use in patients with breast cancer, and additional studies are underway to expand their applicability. However, low concentrations of circulating tumor DNA and the necessity for standardization across different platforms remain a challenge for the expanded application. In this review, we present an overview of the genetic variants detected in circulating tumor DNA from patients with breast cancer, emphasizing their potential utility in guiding personalized therapeutic strategies and predicting treatment responses across the diverse molecular subtypes of the disease.</p>