Uromastyx is a genus of the herbivorous agamid lizards, also known as spiny-tailed lizards or mastigures, which are found in parts of Africa and the Middle East. Currently, several species of this genus are available in the international pet trade in Japan. In this study, two imported wild-caught spiny-tailed lizards (Arabian blue mastigure, Uromastyx ornata philbyi, and Sudan mastigure, Uromastyx dispar flavifasciata) were diagnosed with a Cryptosporidium (Apicomplexa: Cryptosporidiidae) infection based on the presence of the oocysts in the rectal feces using sucrose flotation and light microscopy examination at a local animal hospital in Tokyo, Japan. One of the lizards had died, and histopathological examination revealed enteritis with the Cryptosporidium parasite. Sequence analyses using the small subunit ribosomal RNA, actin, and 70-kDa heat shock protein genes indicated that the lizards had contracted a novel variant of C. avium that commonly infects avian species.