The extracellular matrix (ECM) is an important compartment of tumor biology. It modulates tumor cell proliferation, differentiation and migration, thus contributing to tumor growth and metastasis. ECM has also been hypothesized to participate in cell transformation. Furthermore, tumor ECM and fibrosis poses a tissue limiting barrier for the effective penetration of targeted therapies. As such, we have investigated the effect of a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor fluvastatin on the basal expression of ECM components (e.g. fibronectin, collagen IV) in cultured human (MDA-MB-231) and mouse (3LL) tumor cells. We have also characterized the proapoptotic and cell cycle modulating effects of fluvastatin in these cells in order to determine the cellular scenario in which the ECM gene expression modulation occurs, and its potential relationship with these processes. The basis for this is that fluvastatin (statins in general) prevent the synthesis of mevalonate, the precursor of geranylgeranyl pyrophosphate and farnesyl pyrophosphate which are necessary for the prenylation and activation of many Ras and Rho family proteins. Ras proteins, in turn, have been shown to be implicated in ECM synthesis in renal and hepatic tissues. Our results indicate that fluvastatin induces a dose-dependent antiproliferative, cell cycle arresting and cell dettachment effect in both cell lines. Fluvastatin also dose-dependently decreases the transcription of fibronectin and collagen, even at doses which cause a minor or no effect on cell proliferation and viability. All these effects of fluvastatin are reversed by cotreatment with geranylgeraniol but not with farnesol.