Pulmonary histoplasmosis is a granulomatous disease, whose diagnosis is not always easy, as it may simulate metastatic lesions due to similar radiographic findings. We herein report two cases of histoplasmosis with solitary pulmonary nodule in asymptomatic patients with histories of cancer surgeries, whose diagnoses were confirmed by postoperative pathological examinations. Doctors must pay attention to risk factors for immunosuppression such as the histories of chemotherapy, radiotherapy, or malignancy, which may increase chances of developing histoplasmosis. Limited surgical intervention is the treatment of choice for these localized lesions.