Purpose:Strongyloides stercoralis, a worldwide parasitic nematode, can persist indefinitely within a host, usually asymptomatic, through a mechanism known as autoinfection. Immunosuppression may cause rapid increases in the numbers of re-infecting larvae (hyperinfection), which can disseminate throughout the body, usually with a fatal outcome. The diagnosis is made by finding larvae in the stools, but in some patients larvae can be found incidentally in colonic biopsy specimens. The purpose of this study was to review all cases of strongyloidiasis detected in colonic biopsies in patients who had not been suspected of harboring a parasite. Methods: This study was conducted at Caris Life Sciences, a specialized gastrointestinal pathology laboratory receiving specimens from private outpatient endoscopy centers across the U.S. We analyzed electronic data from the Caris database, which includes demographic, clinical, and endoscopic information, site of origin, and histopathologic report for each biopsy. From a series of 515,724 patients who underwent colonoscopy with mucosal biopsies between 1/2008 and 5/2010, we extracted data for all patients who had nematode larvae detected in their colonic biopsies. Results: A total of 13 patients (10 men and 3 women; age range 40-89) had larvae or fragments of larvae consistent with S. stercoralis in the colonic mucosa. Nine patients were from southern states, 2 from the Northeast, and one from the Midwest. The reasons for colonoscopy were screening colonoscopy (8 patients), follow-up of inflammatory bowel disease (2 patients), abdominal pain with diarrhea (2 patients), and a history of rectal ulcer (one patient). Colonoscopy showed polyps in 6 patients, colitis in 4, polyps and colitis in 2, and a cecal ulcer in one patient. Parasitic larvae identified as or suspicious for S. stercoralis were surrounded by intense eosinophilic responses in all patients; in 7 cases the inflammation around the larvae elicited a polypoid inflammatory response. In none of the cases had the infection been known or suspected. Conclusion: Although foci of S. stercoralis endemicity may still exist in the Appalachian region of the U.S., most cases are diagnosed in immigrants from tropical developing areas. Because the infection is extremely uncommon and usually asymptomatic, it is rarely suspected. In our series, it was found unexpectedly in 2/100,000 patients who had a colonoscopy with mucosal biopsies. In patients with clinically manifest colitis it could not be determined whether the parasitic infection was incidental or causative; however, the dense eosinophilic inflammation present in most cases also in areas where parasites were not detected suggests that S. stercoralis may have played an etiologic role.