Silicosis and tuberculosis (TB) are both global health concerns, with high prevalence among miners from the South African gold mines. Although knowledge has accumulated about these two conditions as distinct diseases since the early 20th century, and despite progress in technology with multiple diagnostic tools and treatment options available for TB, the challenge of distinguishing and therefore efficiently managing these two conditions in this population remains as current as it was 100 years ago. To illustrate the diagnostic and health service problems of distinguishing TB and silicosis clinically and radiologically in former gold miners from the South African mines living in resource-poor areas, we discuss four cases reviewed for this report by a panel of experts. For each case, occupational history, past and current medical history, physical examination, radiological and laboratory findings are described. Common themes are: (1) poor agreement between radiological and clinical presentation; (2) poor agreement between radiology findings and detection of active TB on sputum Xpert MTB/RIF testing; and (3) difficulty in distinguishing the clinical and radiological presentations of silicosis and tuberculosis. Possible consequences at the population level are undertreatment or overtreatment of TB, and underdiagnosis or overdiagnosis of silicosis. There is a need for training of practitioners who are screening or attending to former gold miners in the clinical and radiological features of combined disease, using a curated database of miners' chest X-ray images.Investment in protocols for management of both acute and chronic silicotuberculosis in ex-miners is needed, as is clinical, epidemiologic, and operations research.