False positive D-dimers are common & lead to an expensive confirmatory work-up. The approach of a highly sensitive assay for screening followed by a highly specific assay for confirmation, commonly used in diagnosing AIDS and Lyme disease, have not been applied to D-dimer testing. We describe a case of a 32-year old female with pleuritic chest pain and a D-dimer of >2000µg/l. Although negative chest CT and leg ultrasound for thromboembolism were performed, persistent pleuritic chest pain mandated further work-up. We used a confirmatory D-dimer assay with much higher specificity to declare the first test false positive. Such a negative confirmatory test can save further follow-up, work-up, and anxiety on both the parts of patient and physician, and should be considered in diagnostic algorithms of venous thromboembolism.