A revision of Nemocardium Meek 1876 from the Mediterranean Plio-Pleistocene has led to the recognition of two species, Nemocardium (N.) cyprium (Brocchi 1814) and Nemocardium (N.) italicum nom. nov. Both species are poorly known and with a complex history of misidentifications. Brocchi’s holotype of Venus cypria, from the Early Pliocene deposits of Siena (Italy), is the only specimen of Nemocardium (N.) cyprium so far known. Nemocardium (N.) italicum occurs in fine-grained deposits, ranging from the Early Pliocene to the Early Pleistocene. Both in the old and in the modern literature, this species has been misidentified as Cardium striatulum Brocchi 1814, which is synonym of Laevicardium crassum (Gmelin 1791). Nemocardium was notably diverse in the Eocene and Oligocene of England, France and Italy. The occurrence of Nemocardium in the Neogene-Pleistocene of Europe is a case of biogeographic disjunction, due to the closure of the eastern seaway to the Indo-Pacific in the late Early Miocene. As a consequence of the climatic cooling through the Cenozoic and Quaternary, Nemocardium underwent a dramatic drop in diversity. Its persistence in the Mediterranean till the Early Pleistocene, with Nemocardium (N.) italicum, was probably due to favourable climatic conditions in this basin. Nemocardium (N.) bechei (Reeve 1847) seems to be the sole living species, mainly distributed in the tropical waters of the Indo-Pacific.