Subclavian vein thrombosis is an uncommon clinical condition which is often associated with venous catheterization or secondary to excessive effort. We present a 54-year-old female with subclavian vein thrombosis as a first presentation of renal cell carcinoma. Although this is an unusual presentation, malignancy should be considered in the differential diagnosis. Hypercoagulability as part of a paraneoplastic syndrome was considered a possible etiology. In patients with otherwise unexplained subclavian vein thrombosis, full systemic examination and radiological evaluation of the abdomen, retroperitoneum and pelvis should be pursued. A review of the literature relevant to this unusual case is provided.