Chylothorax is defined as the presence of chyle in the pleural cavity. Central vein thrombosis is an under-recognized cause of chylothorax in the adult population and is commonly related to central venous catheterization. Case 1 illustrates a patient with AIDS and disseminated tuberculosis with left chylothorax and central vein thrombosis after a month of antituberculosis therapy. Case 2 was a patient with advanced seminoma who presented with left chylothorax and central vein thrombosis while on chemotherapy. Chylothorax resolved with anticoagulation for both cases. Case 3 was a lymphoma patient with central vein thrombosis who developed chylothorax during chemotherapy. Chylothorax resolved with the continuation of anticoagulation and did not recur despite his progressive underlying lymphoma. There was no central venous catheterization in any of these three cases. These cases illustrate the unique association of central vein thrombosis and chylothorax and the importance of anticoagulation in its management.