Here for the first time we showed, despite the oncogenic mutations in β-Catenin, that TGF-β is a modulator of β-Catenin levels in tumoral fibroblasts as well as non-tumoral fibroblasts. The results show that the TGF-β pathway is active in desmoids cells and in in situ tumors. A dose dependent increase in β-Catenin protein levels was observed after TGF-β treatment in combination with an increased repression of GSK-3β both in normal and tumoral fibroblasts. TGF-β stimulation also led to an altered – up to 5 fold – transcriptional activity of β-Catenin responsive promoters, such as IGFBP6 as well as increase of TOPflash activity. TGF-β stimulation increased cell proliferation and BrdU incorporation 2.5 times. Taken together, we propose that TGF-β is a modulator of β-Catenin levels in tumoral fibroblasts and non-tumoral fibroblasts, despite the oncogenic mutations already present in this gene in tumoral fibroblasts of desmoid tumors. This modulation of β-Catenin levels by TGF-β may be involved in determining the tumoral phenotype of the cells.