Far upstream enhancers are predicted to act by looping and activating general transcription factors on core promoters and to require proximal promoter sequences for appropriate gene activation in time and space. We have previously described an FGF-inducible response element (FiRE) located far upstream on the syndecan-1 gene. The FiRE is activated specifically by members of the fibroblast growth factor (FGF) family in NIH3T3 cells. Here we describe the requirements of syndecan-1 proximal promoter for the activation of FiRE by FGF-2. Transient and stable transfections revealed that neither proximal promoter SP1 sites nor TATA-box are required for the FGF-8 induced activation of FiRE. Notably, the enhancer is activated in both orientations by FGF-8 even in the absence of proximal promoter. Importantly, removal of the promoter did not affect the growth factor specificity of FiRE. Proximal promoter independent activation of syndecan-1 gene by FGF-8 might be required during development when syndecan-1 proximal promoter needs to be largely attenuated but simultaneous transient and rapid FGF-S induced transcription is required.