The impact of Pleistocene climatic fluctuations on the distributions of plant species in the Greater Cape Floristic Region is largely unknown. We used a molecular fingerprinting tool, inter‐simple sequence repeat (ISSR) PCR to examine the spatial distribution of genetic variation in the common and widespread shrub Elytropappus rhinocerotis . We wished to test the hypothesis that refugia for the species were located in areas which were buffered from marked variations in precipitation between glacial and interglacial periods. Populations from less protected areas, in contrast, should have suffered size reductions or extinctions during the dry Holocene optimum. We detected a large amount of genetic variation in the species, which was apportioned largely amongst individuals within populations rather than amongst populations or regions, as expected for an outcrossing and well‐dispersed plant species. However, there was significant spatial structure and an uneven distribution of diversity across the range. Geographic distance is a very poor predictor of genetic distance between localities, especially towards the east of the range. This may be due to range alteration over the time‐scale reflected by ISSR polymorphism. Inter‐SSR variation declined from south to north in the western arm of the range, consistent with the prediction of Holocene aridification starting first and being most extreme in the north. Areas shown by the marker to harbour populations with high levels of variability include most parts of the eastern arm of the range, and the Kamiesberg highlands. Possible explanations for the observed patterns of ISSR variation are discussed. Keywords: Asteraceae, Cape flora, climatic history, Elytropappus rhinocerotis, ISSR, late Quaternary, phylogeography, spatial structure.