Breast cancer is a complex and heterogeneous disease, with molecular profiling revealing subtypes such as luminal A, luminal B, basal-like, HER2-positive, and normal. Breast cancer cell lines, like MCF-7, have been widely used in research, but their ability to reflect this heterogeneity is debated. Recent studies show that cell lines can represent these subtypes, though some, like claudin-low, are over-represented. However, cell lines may not fully capture the complexity of clinical samples, including stromal interactions and tumor microenvironment. Three-dimensional models are increasingly used to better mimic in vivo conditions, improving drug screening and understanding of tumor biology. Despite this, challenges remain, including the need for more diverse models and the inclusion of cancer stem cells. The use of cell lines must be carefully evaluated to avoid misleading data. Additionally, some cell lines, like MDA-MB-435, are controversial due to their possible origin from melanoma rather than breast cancer. There is a need for more cell lines representing rare subtypes and male breast cancer. Overall, cell lines remain valuable tools but must be used in conjunction with other models to improve understanding and treatment of breast cancer.Breast cancer is a complex and heterogeneous disease, with molecular profiling revealing subtypes such as luminal A, luminal B, basal-like, HER2-positive, and normal. Breast cancer cell lines, like MCF-7, have been widely used in research, but their ability to reflect this heterogeneity is debated. Recent studies show that cell lines can represent these subtypes, though some, like claudin-low, are over-represented. However, cell lines may not fully capture the complexity of clinical samples, including stromal interactions and tumor microenvironment. Three-dimensional models are increasingly used to better mimic in vivo conditions, improving drug screening and understanding of tumor biology. Despite this, challenges remain, including the need for more diverse models and the inclusion of cancer stem cells. The use of cell lines must be carefully evaluated to avoid misleading data. Additionally, some cell lines, like MDA-MB-435, are controversial due to their possible origin from melanoma rather than breast cancer. There is a need for more cell lines representing rare subtypes and male breast cancer. Overall, cell lines remain valuable tools but must be used in conjunction with other models to improve understanding and treatment of breast cancer.