Our results indicate that TGFBI, which we found secreted by macrophages, mesenchymal tumour cells and CAFs, is a crucial player regulating breast tumour‐ and metastasis‐initiating potential through the modulation of the tumour microenvironment and hypoxia, and emphasise the importance of the extracellular matrix on breast cancer progression and metastasis. Here, TGFBI is linked to neoplasm.