The currently favoured model of the evolution of C4 photosynthesis relies heavily on the interpretation of the broad phenotypic range of naturally growing C3-C4 intermediates as proxies for evolutionary intermediate steps. On the other hand, C3-C4 intermediates had earlier been interpreted as hybrids or hybrid derivates. By first comparing experimentally generated with naturally growing C3-C4 intermediates, and second summarising either direct or circumstantial evidence for hybridisation in lineages comprising C3, C4 and C3-C4 intermediates, we conclude that a possible hybrid origin of C3-C4 intermediates deserves careful examination. While we acknowledge that the current model of C4 photosynthesis evolution is clearly the best available, C3-C4 intermediates of hybrid origin, if existing, should not be used for further analysis of this model. However, experimental C3 x C4 hybrids potentially are excellent systems to analyse the genetic differences between C3 and C4 species and, also using segregating progeny, to study the relationship between individual photosynthetic traits and environmental factors.