Mule deer can be divided into two main groups: the mule deer (sensu stricto) and the black-tailed deer. The first group includes all subspecies, except O. h. columbianus and O. h. sitkensis, which are in the black-tailed deer group. The two main groups have been treated as separate species, but they hybridize, and virtually all recent authorities treat the mule deer and black-tailed deer as conspecific. Mule deer apparently evolved from the black-tailed deer. Despite this, the mtDNA of the white-tailed deer and mule deer is similar, but differs from that of the black-tailed deer. This may be the result of introgression, although hybrids between the mule deer and white-tailed deer are rare in the wild (apparently more common locally in West Texas), and the hybrid survival rate is low even in captivity. Many claims of observations of wild hybrids are not legitimate, as identification based on external features is complicated.

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