Species of the genus Blastocystis, which are single-cell, intestinal protozoan parasites of humans and animals, remain mysterious, with unclear clinical and epidemiologic significance. In recent years, many researchers have suggested a possible connection between Blastocystis spp. infection and chronic urticaria. In the present article, we review the literature and discuss the possible associations between the clinical symptomatology and pathogenicity of this organism in terms of its subtypes, morphologic forms, genetic diversity, and interactions with other intestinal microbiota.