Tuberculosis (TB) is a pathology whose control is still unsatisfactory at global level. Traditional diagnostic techniques for active TB diagnosis are inadequate: the diagnostic gold standard is the cultural exam which suffers from lengthy processing and requires highly specialized laboratories. This study analyzed the diagnostic sensitivity of the tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube (QFT-IT) in 135 active, microbiologically confirmed TB cases. Sensitivity was 76% for both tests and reached cumulative levels close to 90%. QFT-IT revealed a statistically higher sensitivity than TST in a group of patients affected by various causes of immunosuppression, but was less sensitive in subjects with low levels of circulating CD4+ cells. The number of circulating CD4+ cells showed a direct correlation with the stimulated IFN-gamma production. QFT-IT also demonstrated a decreased IFN-gamma production, with a significant sensitivity reduction, in patients affected by advanced forms of pulmonary TB.