The national incidence of tuberculosis (TB) is increasing, and hospitals are a site of transmission. We investigated a nosocomial outbreak of TB at a 160-bed community hospital in South Carolina that highlights the central role that primary care physicians must play to control this epidemic.We reviewed medical records to identify potential source cases. We retrospectively evaluated exposures to suspected source patients and the subsequent tuberculin reactivity of the 38 hospital employees who had a previous negative tuberculin skin test and were assigned to the ward where the outbreak began. We also evaluated the out-of-hospital contacts of TB cases.A review of medical records identified one patient who had died of prostate cancer and chronic cavitary pneumonia but was never in isolation nor evaluated for TB. Ward employees who worked while this patient was hospitalized had an increased risk for skin-test conversion (43% [12 of 28] vs 0% [0 of 9]; relative risk undefined; P = .02). Among employees who worked with this patient, skin-test converters worked more shifts with (median, 10.5 vs 7), dispensed more medication to (median 7 doses vs 1), and wrote more notes on (median 18 vs 5) the index patient than did nonconverters. Five of 12 of the patient's close out-of-hospital contacts had newly recognized positive tuberculin skin tests. Among 20 casual contacts, there were no new skin-test conversions.A high index of suspicion, prompt isolation and diagnostic testing of potentially infectious hospitalized patients, and a thorough investigation of contacts of patients with TB are needed to prevent TB transmission.