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Patients with Crohn's disease (CD) of the colon are at risk for colorectal cancer and should be screened for dysplasia and cancer of the colon. Small bowel adenocarcinoma (SBA) is a complication of small bowel CD and carries a poor prognosis. However, there is no screening test for SBA in patients with small bowel CD. The aim of this study was to assess the risk and incidence of SBA in a large prospective cohort of patients with small bowel CD and to compare it with the risk of colorectal cancer in patients with CD involving the colon, recruited in the same cohort.In a nationwide French cohort, 11,759 patients with CD were enrolled by 680 gastroenterologists. The SBA risk was obtained by dividing the observed cases in our cohort to the expected cases in the general population.At baseline, 8222 (69.9%) patients had small bowel CD (either alone or associated with colonic CD); their median follow-up was 35 months (interquartile range, 29–40). Five new cases of SBA were diagnosed, all in patients with small bowel CD, within inflamed areas. Among the 5 patients with incident SBA, 4 died of SBA and 1 is in remission 7 years after the diagnosis of SBA. The incidence rates of SBA were 0.235 per 1000 patient-years (95% confidence interval [CI], 0.076–0.547) among patients with small bowel CD and 0.464 per 1000 patient-years (95% CI, 0.127–1.190) among those with small bowel CD for >8 years. This accounted for approximately 30% of the risk of colorectal cancer in patients with CD of the colon. Patients with small bowel CD and small bowel CD for >8 years had an SBA standardized incidence ratio of 34.9 (95% CI, 11.3–81.5) and 46.0 (95% CI, 12.5–117.8), respectively.SBA in patients with small bowel CD carries a poor prognosis, and its risk is approximately 30% of colorectal cancer risk in patients with CD of the colon. Further studies should determine if small bowel endoscopic screening in high-risk patients is feasible and effective.