Estrogen receptors absence (ER-) has been shown to direct human Invasive Ductal Carcinoma (IDC) toward a more aggressive and malignant state. In this study, we examined the expression and function of TRPM7 in the metastatic ER- breast cancer cells. Clinical relevance was established by immunohistochemistry in ER- IDC tissues samples. We found that TRPM7 expression was higher in the invasive tumoral areas (staining score 2.8 ± 0.2) and invaded lymph nodes (staining score 2.3 ± 0.1) than in the non-invasive tumoral areas (staining score 0.8 ± 0.4). In the highly metastatic MDA-MB-231 cell line, a Magnesium Inhibited Cation (MIC) current was recorded in whole cell patch-clamp and was reduced using siRNA directed against TRPM7. TRPM7 silencing neither affected Ca2+-, Mg2+-homeostasis nor cell proliferation but significantly reduced cell migration (by 68 ± 3 %). Moreover, the heterologous overexpression of zebrafish wild type TRPM7 strongly increased cell migration in the weakly migratory MCF-7 cells and in the MDA-MB-231 cells (2.4 fold increase). This migration increase was not observed when we overexpressed a kinase domain truncated TRPM7 form (TRPM7 Δkinase) in both cell lines, demonstrating the role of the kinase domain in breast cancer cell migration. Furthermore, the use of low and high external calcium concentrations did not affect the migration decrease induced by TRPM7 silencing, suggesting that TRPM7 regulates cell migration independently of calcium entry. We finally observed that TRPM7 silencing had no effect on the focal adhesion kinase (FAK) phosphorylation but reduced the myosin IIA heavy chain phosphorylation (by 41 % ± 14). Taken together, our findings suggest that the chanzyme TRPM7 regulates breast cancer cell migration via phosphorylation of myosin IIA, and independently of the calcium influx. Our data support also the consideration of TRPM7 channel as a novel biomarker and/or possibly a pharmaceutical target of the most aggressive human ER- IDC.