Porcellanidae Haworth, 1825 is a family of marine anomuran crabs distributed throughout tropical and temperate regions of all the oceans, typically littoral and sublittoral waters, with a considerable diversity of lifestyles, habitats and colouration. Pachycheles Stimpson, 1858 and Neopisosoma Haig, 1960 share, among other morphological characteristics, the fragmentation of the lateral carapace walls. The morphology of this body region was key to supporting the establishment of Neopisosoma, which increased uncertainty about the taxonomic status of these genera due to the high intraspecific variation of this character. Our study reconstructs the phylogenetic relationship between Pachycheles and Neopisosoma based on mitochondrial and nuclear DNA sequences to evaluate whether these are valid taxa. While Pachycheles seems to be monophyletic, the position of Neopisosoma mexicanum (Streets, 1871) indicates that the group is polyphyletic, and deserves further investigation. Pachycheles is revealed to be older than Neopisosoma, and likely originated in the Indo-Pacific, later spreading to the American continent during the early Tertiary. Neopisosoma may have arisen much later in the Caribbean Province before the closure of the Isthmus of Panama, explaining its distribution, which is restricted mainly to Central America. The inclusion of a considerable number of species from both genera represents a significant advance in the study of this controversial group. The phylogenetic reconstruction of Pachycheles unveiled clades corroborated by morphology, but also revealed unclear relationships, which may indicate the potential existence of cryptic species.