Background: Postresection intestinal adaptation is an augmented self-renewal process that might increase the risk of malignant transformation in the intestine. Furthermore, patients with short bowel syndrome (SBS) have other characteristics that might increase this risk. Our aim was to determine the incidence of new intestinal malignancy in SBS patients. Methods: We reviewed the records of 500 adult SBS patients identified from 1982–2013. There were 199 men and 301 women ranging in age from 19–91 years. Follow-up from the time of diagnosis of SBS ranged from 12–484 months. A total of 186 (37%) patients were followed >5 years. Results: The cause of SBS was postoperative in 35% of patients, malignancy/radiation in 19%, mesenteric vascular disease in 17%, Crohn’s disease in 16%, and other in 13%. Twenty-eight (6%) patients received growth stimulatory medications. Fifteen percent of patients had a prior total colectomy. Twenty-eight (6%) patients underwent intestinal transplantation, and 115 (23%) patients had a previous abdominal malignancy, including colorectal cancer in 43 patients. Thirty-six (7%) received radiation therapy. Recurrent colon cancer was found in 2 patients, one at a stoma and the other with lung metastases. New colon cancer was found in 1 patient (0.2%), a 62-year-old woman with long-standing Crohn’s disease. Conclusion: The incidence of colon cancer in this heterogenous group of patients with SBS was similar to that of the normal population. This suggests that the risk of developing a new colon cancer in patients with SBS is not increased.