The spider crabs of the genus Pisa Leach, 1814 (Epialtidae: Pisinae) are reviewed in this study based on morphological and molecular data (16S and COI genes). From these results, a new genus, Afropisa n. gen., is established for the clade composed of Pisa carinimana Miers, 1879, Pisa calva Forest and Guinot, 1966 and Pisa sanctaehelenae Chace, 1966 based on carapace morphology, rostrum, pterygostomian tubercles and male gonopod 1. Additionally, Lissa chiragra (Fabricius, 1775) is transferred to Pisa based on morphological (adults and larvae) and molecular evidence. Furthermore, the status of Pisa hirticornis (Herbst, 1804) is discussed and clarified. The phylogenetic relationships between several Pisinae Dana, 1851 genera, as revealed by molecular data, are discussed. An illustrated identification key of eastern Atlantic and Mediterranean species of Pisinae is provided.