- Controlled hand-cross-pollinations were performed among the genera Hylocereus, Selenicereus, and Epiphyllum and synthetic intergeneric hybrids were obtained. Parental lines and the intergeneric hybrids were studied for their nuclear DNA (2C) content and for their morphological and phenological characteristics. Hybrids between Hylocereus and Selenicereus species produced viable seeds, a finding that showed the lack of post-zygote barriers. Partial to complete sterility was observed in the intergeneric Epiphyllum × Selenicereus hybrids. The dominant relationship between the alleles controlling morphological and phenological traits was elucidated. Among the traits studied, the presence of spines and/or hairy-spines on the fruit peel, the co-dominance of the ripening time, and the dominance of the high number of shoot ribs were the most significant characteristics proving hybridization. Further development of species-specific molecular markers will be valuable for a suitable taxonomic description of these species and for future breeding and genetic studies of these genera with high horticultural potential.