<p dir="ltr">Breast cancer, the leading cause of cancer-related deaths in women, exhibits high metastatic potential to organs such as lymph nodes, lungs, liver, bone, and brain. While early-stage breast cancer has a favorable prognosis, survival rates drop sharply with lymph node involvement and distant metastasis, emphasizing the need to understand metastatic mechanisms, particularly in Triple-Negative Breast Cancer (TNBC).</p><p dir="ltr">Our study explored the role of Lymph-Circulating Tumor Cells (LCTCs) using female nude/NSG mice with MDA-MB-231 cells and BALB/c mice with 4T1 cells as experimental models. Fluorescence Microscopy and Flow cytometry analyses indicated a possibility that Circulating Tumor Cells (CTCs) might utilize the lymphatic system as a metastatic pathway, with lymphatic trafficking potentially preceding organ colonization. Lymph nodes could serve as critical intermediaries in metastatic dissemination rather than passive conduits. Organ-specific analysis following tissue collection demonstrated that CTCs maintained their aggressive phenotype while exhibiting adaptations to distinct microenvironments. Furthermore, the lymphatic system may provide a supportive niche for CTC survival and migration, underscoring its role in facilitating metastasis.</p><p dir="ltr">These findings suggest that targeting lymphatic trafficking and lymph node colonization could provide novel strategies for managing TNBC metastasis. Additionally, understanding the organ-specific tropism of LCTCs could inform personalized therapies and improve prognostic tools, paving the way for targeted interventions in aggressive breast cancer.</p>