Using a transmission electron microscopy-based approach, this study details the striking similarities between Cryptosporidium parvum and the gregarines during in vitro axenic development at high ultra-structural resolution. C. parvum zoites displayed three unusual regions within uninucleated parasites: epimerite-like, protomerite-like, and the cell body; these regions exhibited a high degree of morphological similarity to gregarine-like trophozoites. The presence of a mucron-like bulging structure at the side of the free ovoid gregarine-like zoites was observed after 2 h of cultivation. An irregular pattern of epicytic-like folds were found to cover the surface of the parasites 24 h postcultivation. Some extracellular stages were paired in laterocaudal or side-side syzygy, with the presence of a fusion zone between some of these zoites. The present findings are in agreement with phylogenetic studies that have proposed a sister relationship with gregarines. Cryptosporidium appears to exhibit tremendous variety in cell structure depending on the surrounding environment, thereby mimicking the "primitive" gregarines in terms of the co-evolution strategy between the parasites and their environments. Given this degree of similarity, different aspects of the evolutionary biology of Cryptosporidium need to be examined, considering the knowledge gained from the study of gregarines.