During the summer of 2005, four cases of active tuberculosis from the same occupational setting were investigated in Manchester, UK. The index case had been diagnosed in December of the previous year. At that stage the closest occupational contacts had been screened, all of whom were assessed as being free from active disease, and none had met nationally recommended criteria for chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work contacts developed progressive primary extrapulmonary (pleural) TB. Following a detailed risk assessment, the screening programme was widened to include 137 staff who worked at the job centre (employment agency) where the first four cases had been found. This screening programme was based on tuberculin Mantoux testing, CXR and gamma-interferon testing. Of these 137 contacts screened, one additional person was found to have active disease and six others were offered chemoprophylaxis for LTBI. The isolates from the index case and the first two secondary cases were indistinguishable on VNTR-MIRU (variable number tandem repeat--mycobacterial interspersed repetitive unit) typing at 15 loci. No samples were available for testing from the fourth case of active disease. Management of this incident has benefited from the evolving fields of both genotyping and diagnostic testing for LTBI. However, further research into the epidemiological inferences made through genotyping, as well as the significance of a positive gamma-interferon test in assessing the risk of development of active disease, is still required.