The subfamily Cantharidinae Gray, 1857 (Trochoidea: Trochidae) includes 23 recognized genera and over 200 known living species. These marine top shell snails are microphagous grazers that generally live in shallow rocky shores and in macroalgae and seagrass beds of sub-tropical and temperate waters from the Central and Western Indo-Pacific biogeographic regions to the Mediterranean Sea and the Eastern Atlantic Ocean. Recent molecular phylogenetic studies revising the family Trochidae supported the monophyly of the subfamily Cantharidinae and its sister group relationship to the subfamily Stomatellinae. These studies and others has thus far mostly focused on Indo-Pacific members of the subfamily Cantharidinae whereas here, we investigated phylogenetic relationships among their counterparts from the Mediterranean Sea and the North-eastern (NE) Atlantic Ocean including 33 species of genera Gibbula, Jujubinus, Phorcus, Clelandella, and Callumbonella. The Mediterranean and NE Atlantic taxa were supplemented with 30 Indo-Pacific Cantharidinae species plus 19 members of the sister group subfamily Stomatellinae. Phylogenetic trees were constructed using Bayesian inference and maximum likelihood with two datasets comprised of partial sequences of four or six mitochondrial (cox1, rrnL, rrnS, and cob) and nuclear (28S rRNA and histone H3) genes. A clade comprised of all Mediterranean and NE Atlantic taxa was recovered with high support, but its sister group among the Indo-Pacific lineages could not be determined with confidence (although the assignment of "Trochus" kotschyi to Priotrochus could be rejected). Within the Mediterranean and NE Atlantic clade, genera Phorcus and Jujubinus were recovered as reciprocally monophyletic, and the deep-sea genera Clelandella and Callumbonella were placed with high support as sister to Jujubinus. However, the genus Gibbula as currently defined was not monophyletic and constituent species were divided into three major clades and two independent lineages. Phylogenetic relationships among Phorcus, Jujubinus (plus Clelandella and Callumbonella), and the different clades of Gibbula were not fully resolved but received higher support in the phylogenetic analyses based on six genes. A first approach to resolve phylogenetic relationships within Stomatellinae was conducted showing that the diversity of the subfamily is highly underestimated at present, and that Calliotrochus is possibly a member of this subfamily. A chronogram was reconstructed using an uncorrelated relaxed lognormal molecular clock and the origin of the Mediterranean and NE Atlantic clade was dated right after the Azolla phase in the Middle Eocene about 48 million years ago whereas diversification of major clades (genera) followed the eastern closure of the Tethys Ocean in the Middle Miocene about 14 million years ago.