This study focused on clarifying phylogenetic relationships and evolution within Caricaceae. Our phylogenetic analysis based on nucleotide sequences from the ITS of the ribosomal DNA and three chloroplast fragments (matK, trnL-trnF, and psbA-trnH) included 29 taxa belonging to five genera: the neotropical genera Carica, Vasconcellea, Jarilla, and Jacaratia and the equatorial African genus Cylicomorpha. Having a relatively low mutation rate, matK, and trnL-trnF were used for estimating relationships at the generic level, while intrageneric evolution within Vasconcellea was studied with the more variable ITS and psbA-trnH sequences. Gaps, coded as binary characters, were added to the sequence alignments before performing Maximum Parsimony and Maximum Likelihood analyses. Monophyly of Caricaceae as well as phylogenetic distance between Carica and Vasconcellea species, previously belonging to the same genus, and monophyly of the resurrected genus Vasconcellea were emphasized. Within Vasconcellea, the largest genus of this family, two well-confirmed evolutionary lineages could be discerned: (1) V.xheilbornii, V. weberbaueri, V. stipulata, and V. parviflora and (2) a clade holding all other taxa of the genus. Incongruence between nuclear ITS and chloroplast psbA-trnH datasets, shown to be significantly caused by some taxa of the genus Vasconcellea, indicated that reticulate events in this genus might be more frequent than previously suspected. Moreover, intra-individual ITS sequence heterogeneity provided further evidence for the hybrid or introgressed origin of different taxa and one presumed hybrid belonging to this genus.