Malignancy is associated with a high risk of venous thromboembolism (VTE), and treatment with anticoagulant therapy is associated with a high risk of bleeding. Thus, accurate and timely VTE diagnosis in cancer patients is essential for identifying individuals who would benefit from anticoagulant therapy and for avoiding unnecessary treatment that can cause anticoagulant-related bleeding. The approach to the diagnosis of VTE in non-cancer patients involves a stepwise process beginning with an assessment of the pretest probability (PTP) of VTE using a validated clinical prediction rule (CPR) followed by D-dimer testing and/or diagnostic imaging. In patients with a low PTP and a negative D-dimer result, VTE can be excluded without additional imaging. However, published data suggest that CPRs and D-dimer testing may not be as accurate or as useful in patients with cancer. Studies have shown that the combination of a low PTP and negative D-dimer result is not efficient for exclusion of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the cancer patient population because the vast majority of patients still require radiologic imaging. We propose that cancer patients with suspected VTE should proceed directly to radiologic imaging to confirm or exclude a diagnosis of DVT or PE.