Numerous studies, performed in recent years, have provided the convincing demonstration that the incidence of newly diagnosed malignancy is increased among patients with unexplained venous thromboembolism during the first 6 to 12 months after the thromboembolic event. Among malignancies presenting with venous thromboembolism as a first clinical manifestation, prostate and colorectal cancer are the most commonly identified. Other common sites are cancer of the lung, pancreas, stomach, ovary, brain, and bladder. Extensive screening with computer tomography scanning, gastrointestinal endoscopy, and a number of tumor markers have the potential to detect occult malignancies. However, whether an extensive diagnostic work-up in all patients presenting with unexplained venous thromboembolism is cost-effective still remains to be demonstrated.