An association between thymic cyst and thymic epithelial malignancy has been previously reported. However, several case studies have reported granulomas in the thymus with high metabolic activity, mimicking thymic malignancy. Additionally, an inflammatory response provoked by the rupture of cyst walls has been proposed as a pathogenesis of cholesterol granuloma in the thymus. However, the natural growth history of thymic granuloma remains unclear. We herein report the first case demonstrating the natural growth history of a thymic granuloma adjacent to a thymic cyst. Ten-year follow-up of the thymic cyst revealed a growing nodular lesion with high metabolic activity adjacent to the cyst. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed a maximum standardized uptake value of 12.1 in a 2.5-cm solid mass. We performed total thymectomy given a high suspicion of a malignant thymic epithelial tumor. Histopathologic examination revealed a cholesterol granuloma in the thymus, which was directly connected to the thickened region of the cystic wall through a rupture of the wall. This case highlights the importance of considering thymic granuloma as a differential diagnosis for a growing anterior mediastinal nodule with high metabolic activity. Further, the clinical course and histopathologic findings of this case provide supporting evidence for the proposed pathogenesis of thymic granuloma.