This work describes and analyses the December 2004 rockslide that affected the working face of the Ca’ Madonna quarry (Municipality of Urbania, Province of Pesaro and Urbino, Italy), where limestones are extensively quarried for aggregates. The landslide occurred along an unsurveyed, approximately 10-cm thick clayey intra-bed layer that mainly consists of smectite-group clayey minerals. Laboratory analyses indicate that it is very active and shows a high capacity to absorb water until reaching a swelling pressure of up to 1200 kPa. Mining activities reduced lithostatic load and facilitated rainwater infiltration down to this bentonitic layer, which led to fully softened conditions with a resulting severe reduction in the shear strength parameters. Under such conditions, the slope stability back-analysis was performed by the limit equilibrium method, considering a planar rock slope failure with tension cracks and with different water level heights. The results show that a small increase of water pressure was sufficient to exceed the factor of safety. Stratigraphically, this layer can be correlated with the Lower Campanian Bentonitic Layer already reported in other sites of Central Italy. Therefore, the potentially great spatial extent of this layer and the possibility that the reported conditions may occur in other similar settings, make it important to identify its presence in order to prevent analogous situations.