We have previously shown that 2 human melanoma cell lines, the metastatic HT‐144 and the non‐metastatic SK‐Mel‐2 cells, exhibit marked in vitro heterogeneity with respect to integrin expression, migration and invasion potential. Here, we provide evidence that HT‐144 melanoma cells, but not SK‐Mel‐2 cells, undergo a reversible transition to a fibroblastoid morphology following treatment with either their own serum‐free acidified conditioned medium or biologically active exogenous TGF‐β1, thus identifying TGF‐β as an autocrine regulator of the spindle shape morphology of HT‐144 melanoma cells. The fibroblastoid phenotype correlated with up‐regulated β1 and β3 integrin and down‐regulated E‐cadherin expression, as shown by flow cytometry, Western blot and RT‐PCR, as well as up‐regulated expression of the matrix metalloproteinase MMP‐9, as demonstrated by zymography. Our data further illustrate the TGF‐β1‐dependent up‐regulation of integrin‐linked kinase and the nuclear translocation of β‐catenin, 2 intracellular proteins involved in integrin and cadherin signaling. Int. J. Cancer 83:255–262, 1999. © 1999 Wiley‐Liss, Inc.