Colon polyps are commonly detected in the workup of fecal occult blood (FOB). It is, however, unclear whether colon polyps can adequately explain FOB. Our aim was to determine the frequency of upper gastrointestinal (UGI) pathology in patients with and without UGI symptoms and with and without risk factors for UGI pathology (such as smoking, drinking alcohol, taking nonsteroidal anti-inflammatory medications, or the presence of associated chronic diseases) who have colon polyps and FOB. Among our 67 study patients with colon polyps and FOB, 79% had associated UGI lesions. Presence or absence of UGI symptoms, risk factors associated with UGI lesions, and polyp characteristics such as size, location, number, and histology, did not appreciably affect this high frequency. Ulcers were the most common lesions in both symptomatic and asymptomatic patients. We conclude that patients with colon polyps found in the evaluation of FOB are likely to have concomitant UGI pathology, and UGI workup should be considered in both symptomatic and asymptomatic patients.