Thromboembolism (TE) is frequently encountered in patients with cancer, also in those with leukemias, depending on type of disease and treatment. Assessing risk of TE in individual patients remains challenging. Laboratory testing could help in individual risk assessment, but in practice, only ruling out TE is being done with the help of a d-dimer test. No tests are sufficiently robust to identify high risk patients. In this presentation I want to address the reasons for the apparent and disappointing lack of diagnostic tools to pick up high risk for TE patients (mostly venous, but also arterial TE events). I propose strategies to increase the diagnostic yield of coagulation targeted laboratory tests and sketch a perspective for diagnostic profiling and, where possible, timely and individually tailored antithrombotic intervention.