A second primary malignancy (SPM) is frequently reported in patients with a gastrointestinal neuroendocrine tumour (NET). The majority of SPM are located in the gastrointestinal tract, but malignancies at other sites are described as well. This phenomenon might just be coincidental due to high incidence rates of asymptomatic NET lesions in patients who are operated or who undergo autopsy for another primary malignancy. However, other theories have been developed since the observed incidences rates seem to be double as high as expected. Some authors suggest a common genetic predisposition, while others report tumourigenic properties of various neuroendocrine peptides, including secretin, gastrin and cholecystokinin. This review is illustrated by a case report of a patient in whom the radiological diagnosis of a diffuse liver metastasized adenocarcinoma of the rectum changed dramatically after positron emission tomography and explorative laparoscopy to a curable adenocarcinoma of the rectum with a simultaneous well-differentiated neuroendocrine carcinoma.