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Aim: Fibulins and ADAMTSs are two families of extracellular matrix proteins implicated in key functional and pathological processes. The fact that the fibulin-1 and ADAMTS-1 proteins interact raises new questions about the roles of these extracellular matrix proteins in modulating tumor progression. Herein, we described the functional implications of the interaction between fibulin-1 and ADAMTS-1 on the behavior of breast cancer cell lines. Methods: Fibulin-1 and ADAMTS-1 were exogenously expressed in MCF-7 and MDA-MB-231 cell lines to assay the effect of their interaction in cellular properties. Results: ADAMTS-1 expression exacerbates tumor effects in terms of proliferation, invasion and mammosphere formation. In contrast, the simultaneous expression of ADAMTS-1 and fibulin-1 impairs these effects. The analysis of the expression of both proteins in human breast cancer tissue arrays provides new insights into the complex roles of fibulin-1 and ADAMTS-1 in this type of tumor. Conclusion: Our results suggests that the interaction between ADAMTS-1 and fibulin-1 induces a pronounced anti-tumoral effect.