Solanum series Conicibaccata is the second largest series in section Petota, containing 40 species widely distributed from southern Mexico to central Bolivia. It contains diploids (2n = 2x = 24), tetraploids (2 = 4x = 48) and hexaploids (2n = 6x = 72), and the limited number of species examined have been shown to be allopolyploids. Previous morphological and molecular studies using plastid DNA failed to discriminate clear species boundaries. Conserved orthologous nuclear DNA sequences (COSII) were used to compare the relationships among 72 accessions from 22 species from series Conicibaccata and 42 additional accessions from related series. The results supported previous studies showing the diploid members of series Conicibaccata to be related to other South American “clade 4” species, and showed all of the polyploids to be allopolyploids among members of clade 4 and other South American species of “clade 3” (series Piurana and related species). Low bootstrap support values and morphological similarity suggest recent origins and the need for a reduction in number of recognized species in series Conicibaccata.