Focal reactive overgrowths of oral mucosa were investigated in the following groups: gingival pyogenic granuloma, fibrous epulis, calcifying fibrous epulis, peripheral giant cell granuloma, giant cell fibroma, fibroepithelial polyp and denture-related fibrous hyperplasia (n = 8 for each group). We hypothesised that immunoreactivity to tenascin-C, a functional protein associated with connective tissue organisation and cell migration, would be differentially distributed in individual lesions and between lesion groups. Staining patterns for giant cell fibromas and fibroepithelial polyps were similar to those reported for normal mucosa. By contrast, additional staining was observed in the other lesion groups, although immunoreactivity was variable and not specific to each lesion group. Strong immunoreactivity was observed around blood vessels lined with plump endothelial cells and in regions where keratinocytes were migrating over ulcerated surfaces. Interlacing collagenous fascicles could be either strongly or weakly immunoreactive, with either fibrillar or diffuse staining. Localised staining was observed around, but not within, areas of calcification.