Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk–benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug–drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.