Background: Studying the pathogenic potential of Blastocystis spp. by in vitro and in vivo experimental studies led to suspicions concerning its role in development of cancer colon. Still, this hypothesis remains under investigations. Objective: To investigate the pathology induced in the gut of mice inoculated with Blastocystis spp. isolates derived from patients with and without colorectal carcinoma (CRC). Subjects and Methods: Seven Blastocystis spp. isolates were derived from patients with CRC, six from non-CRC patients with symptomatic blastocystosis and six from non-CRC asymptomatic Blastocystis spp. carriers. Isolates were used to induce experimental blastocystosis in three groups of three-weeks-old BALB-c mice: GI was inoculated by CRC isolates; GII by symptomatic non-CRC isolates; and GIII by non-CRC asymptomatic isolates. Always, one clinical isolate was used to infect one mouse. Each group contained one negative control mouse inoculated with parasite-free culture medium, kept under the same conditions. Results: Histopathological examination of sections of intestine of all inoculated mice in the three groups showed positive infection with parasites seen only in the cecum and colon, no parasites were seen in the small intestine. Inflammatory cells infiltrations were detected in mice of the three groups with varying degrees. Vacuolar forms of Blastocystis spp. were seen infiltrating the submucosa in sections from mice in GI (4 mice) and GII (2 mice) but not in GIII. The significant difference in the pathologic changes induced in the intestine of mice in the three groups was observed being more severe with polypoid formation in mice in GI (4 mice) than in GII (1 mouse). Conclusion: Blastocystis spp. isolates associating CRC differ in their proliferative and invasive pathogenic capabilities than symptomatic isolates. Asymptomatic Blastocystis spp. are non-invasive organisms causing only mild inflammatory response in the large intestine of experimentally infected animals