In 2011, the Spanish Society of Medical Oncology (SEOM) first published a clinical guideline of venous thromboembolism (VTE) and cancer. This guideline was updated in 2014, and since then, multiple studies and clinical trials have changed the landscape of the treatment and prophylaxis of VTE in cancer patients. To incorporate the most recent evidence, including data from direct oral anticoagulants (DOACs) randomized clinical trials, SEOM presents a new update of the guideline.