Premise of the Study: The species boundaries of wild and cultivated potatoes are controversial, with most of the taxonomic problems in the cultivated potato clade. We here provide the first in-depth phylogenetic study of the cultivated potato clade to explore possible causes of these problems. Methods: We examined 131 diploid accessions, using 12 nuclear orthologs, producing an aligned data set of 14,072 DNA characters, 2171 of which are parsimony-informative. We analyzed the data to produce phylogenies and perform concordance analysis and goodness-of-fit tests. Key Results: There is good phylogenetic structure in clades traditionally referred to as clade 1+2 (North and Central American diploid potatoes exclusive of Solanum verrucosum), clade 3, and a newly discovered basal clade, but drastically reduced phylogenetic structure in clade 4, the cultivated potato clade. The results highlight a clade of species in South America not shown before, ‘neocardenasii’, sister to clade 1+2, that possesses key morphological traits typical of diploids in Mexico and Central America. Goodness-of-fit tests suggest potential hybridization between some species of the cultivated potato clade. However, we do not have enough phylogenetic signal with the data at hand to explicitly estimate such hybridization events with species networks methods. Conclusions: We document the close relationships of many of the species in the cultivated potato clade, provide insight into the cause of their taxonomic problems, and support the recent reduction of species in this clade. The discovery of the neocardenasii clade forces a reevaluation of a hypothesis that section Petota originated in Mexico and Central America.