The purpose of this study was to compare the morphologic characteristics of the "reversed halo" sign caused by tuberculosis with those caused by cryptogenic organizing pneumonia (COP) and to determine whether high-resolution CT (HRCT) can differentiate between these two conditions. We retrospectively reviewed the HRCT scans of patients with the reversed halo sign caused by active tuberculosis and HRCT scans of patients with the reversed halo sign caused by COP. The study included 12 patients with active pulmonary tuberculosis (10 women and two men) and 10 patients with biopsy-proven COP (five women and five men). Tuberculosis was diagnosed by culture of sputum, bronchoalveolar lavage, or biopsy specimen. All patients underwent HRCT, and the images were reviewed by two chest radiologists who reached decisions by consensus. HRCT scans of all patients with active tuberculosis showed reversed halos with nodular walls; in most cases (10/12), we also observed nodules inside the halos. None of the HRCT scans of the COP cases reviewed had halos with nodular walls or nodules inside them. We also observed parenchymal abnormalities, such as consolidation, ground-glass, and linear opacities, associated with the reversed halo sign. Neither the number of reversed halo sign lesions nor the associated parenchymal lesions discriminated between tuberculosis and COP. Nevertheless, the association of the reversed halo sign with nodular walls or nodules inside the halo was seen only in tuberculosis patients. Although COP is considered the most frequent cause of the reversed halo sign, the presence of nodular walls or nodules inside the reversed halo strongly favors a diagnosis of active pulmonary tuberculosis rather than COP.