Introduction: It is already well-known the frequent asso ciation of infectious endocarditis due to Str. gallolyticus with colorectal premalignant or malignant lesions. Sometimes, the clinical manifestations of subacute infectious endocarditis may be concealed by neoplasia and may be confused with various paraneoplastic manifestations. Methods: We present a 75 year old patient with multiple comorbidities (hypertension, type 2 diabetes mellitus, stable angina), admitted for significant weight loss, inappetence, diarrhea alternating with constipation and non-specific neuropsychiatric disorders (somnolence, memory disturbances, depression). Results: Colonoscopy showed a tumor of approx. 1 cm on the ileo-cecal valve and the initial histopathological examination revealed only high-grade dysplasia. Computer tomography exam (CT) showed no intracerebral, intra-thoracic or intra-abdominal metastases. Echocardiography revealed large vegetation on aortic valve with mild to moderate aortic insufficiency. Blood cultures (2 to 12 hours apart) were positive for Str. gallolyticus. Given the major embolic risk, the aortic valve surgery was recommended. However, the presence of endoscopically unresectable colonic lesion requires its surgical cure, before the cardiovascular intervention. Conclusions: This case underlines the importance of screening for infectious endocarditis in patients with colonic lesions and atypical clinical manifestations and the multidisciplinary approach of such a case.