PURPOSE: Analysis of gene expression profiles in peripheral blood cells has been explored as an approach for early detection of breast cancer. Thus, we aimed to evaluate the diagnostic and prognostic potential of LIF expression in the peripheral blood of women with breast cancer. METHODS: A total of 121 women over 18 years of age with breast cancer and 80 healthy women were included. Peripheral blood samples were collected from patients at diagnosis and during chemotherapy treatment, as well as samples from healthy women for comparison. LIF expression was evaluated by qPCR. RESULTS: LIF expression does not differ between patients and healthy women, ruling out its use as a liquid biopsy diagnostic tool for this disease. However, LIF expression increases during treatment in patients with positive progression and luminal tumor subtype, suggesting its potential as a prognostic marker. To reinforce this result, there was a negative correlation between LIF and HIF-1α and LIF and heparanase expression in blood, and LIF blood expression and a prognostic tumor score, all known markers associated with an unfavorable prognosis. CONCLUSION: An increase in LIF expression in patients with negative disease progression suggests its potential as a therapeutic response indicator, particularly for those with the luminal tumor subtype. The negative correlation between LIF, HIF-1α, and heparanase provides new insights into LIF's role in breast cancer progression, with potential clinical implications for treatment monitoring. Elevated LIF expression in blood samples may reflect its interaction in tumorigenesis, immune regulation, and the tumor microenvironment.