Reddish mud-rich sediments are common in several karst areas, in the form of red surface soils and clastic cave infillings. The origin and significance of red surface soils have been much debated over recent years, while clastic mud-rich sediments in cave environments have received less attention from geoscientists. The genetic relationship between these two materials still remains uncertain. Because these sediments are mainly composed of fine-grained materials, their study has been generally focused on the clay fraction only. This paper compares the clay fraction of red surface soils and mud-rich cave sediments in the Montagnola Senese karst massif. Previous studies have demonstrated that, in this area, red cave muds originate from the erosion of the similarly red surface soils, that were subsequently re-deposited in the cave environment. Despite these well-established genetic relations, notable differences in the clay fraction of these two materials have been recognized in the present study. These differences are likely to be attributable to the different grades of pedogenetic weathering that affected the two materials. This study demonstrates that the genetic relationship between mud-rich cave sediments and red surface soils can be misinterpreted when only the clay mineral fraction is considered.