Blastocystis spp. are the most common eukaryotic protist encountered in the gut of both humans and many animals [1]. The organism has been diagnosed in both patients with non-specific gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal pain, flatulence, and in asymptomatic individuals [2-4]. Infection has been associated with a variety of diseases such as irritable bowel syndrome (IBS) [5-9] , non-specific colitis, chronic inflammatory bowel disease (IBD) including Crohn's disease and ulcerous colitis [10,11] , and with CRC [12-14]. It has been diagnosed in association with non-gastrointestinal disorders such as skin rash and chronic urticaria [15-18] , as well as Hashimoto's thyroiditis [19]. Because of these discrepancies in associations, and despite the application of recent advances in immunological and molecular methods to Blastocystis spp. research, the pathogenicity of Blastocystis spp.is still controversial and inconclusive [11,20]. The pathogenic potential of Blastocystis spp. has been investigated by in vitro as well as in vivo experimental studies [21]. In vitro studies demonstrated the induction of apoptosis in cell lines [22,23] in contrast to the proliferation of human colonic cancer cell line, HCT116, when incubated with Blastocystis spp. organisms [24,25]. In vivo studies demonstrated pre-neoplastic changes with the formation of aberrant crypt foci in the colon of Blastocystis spp. experimentally infected rats [6]. These studies led to suspicions of Blastocystis spp. as a cause of cancer colon. However, until recently this view remains to be under investigation [20]. The pathological lesions produced in animals by Blastocystis spp. isolates derived from asymptomatic and symptomatic infected humans with gastrointestinal manifestations [27-30] , and from patients with IBS [7,31,32] have been studied and compared. The present study aims to investigate the pathology induced in the gut of mice inoculated with Blastocystis spp. isolates derived from patients with and without CRC to discover the possible oncogenic potential of the parasite.