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Background: Crohn’s disease (CD) is a well known precancerous condition. Late diagnosis of cancer in CD often occurs and the prognosis is poor. The aim of this study was to assess the relationship between clinical presentation and diagnosis of intestinal adenocarcinoma in CD. Patients and methods: Medical records of 12 consecutive patients with intestinal adenocarcinoma in CD and of 79 consecutive CD patients undergoing bowel surgery from 2004 till 2008 were reviewed. Gender, age, disease duration, phenotype and localization, familiarity for colorectal cancer, weight loss, overt rectal bleeding, urgency, vomiting, obstruction, fever, abdominal mass at palpation, abdominal pain, diarrhea, mucorrhea and urinary symptoms were analyzed as possible predictors. Univariate and multivariate logistic regression analyses were performed. Results: Ten men and 2 women underwent surgery for intestinal cancer in CD with a median age of 50 years (31-68). Carcinomas were localized in the terminal ileum in 4 cases, right colon in 3, transverse colon in 1, sigmoid colon in 1, rectum in 2 and an anorectal fistula in 1. Only 3 patients were pre-operatively diagnosed with cancer while the others had a post-operative diagnosis. At diagnosis only 3 (25%) patients presented with AJCC stage II cancer while 4 (33%) presented with stage III and 5 (42%) with stage IV. Rectal bleeding (OR 0.385 (95% CI 0.077-1.926), p=0.20) and weight loss (OR 0.667 (95% CI 0.313-1.418), p=0.17) were unrelated to cancer diagnosis. At univariate analysis age, fever, obstruction, diarrhea and vomiting resulted to be significantly associated to cancer diagnosis. At multivariate analysis only age (OR 1.057 (95% CI 0.999-1.107), p=0.05) and obstruction (OR 6.530 (95% CI 1.533-27.806), p=0.01) significantly predicted cancer diagnosis. Discussion: In CD, rectal bleeding, the most common alarm symptom for intestinal cancer, is not useful for an early diagnosis. CD patients presenting with an older age and obstruction should be thoroughly investigated to rule out neoplastic lesions. Early diagnosis of intestinal cancer remains a clinical challenge in CD.