Fine needle aspiration (FNA) has proven valuable in diagnosing tuberculous lymphadenitis in countries with endemic mycobacterial infection (MI). Its role in developed countries, where sensitivity and positive predictive value are likely to be lower, has not been adequately explored. This retrospective, five-year study from a public hospital in the United States examined the predictiveness of 238 nodal FNAs in patients with MI; 59% of patients were also HIV+. Diagnostic results (stainable acid-fast bacilli or positive culture) were present in nearly half the aspirates; sensitivity was 46%, specificity 100%, positive predictive value (PPV) 100% and negative predictive value (NPV) 94%. If granulomatous inflammation (GI) was also considered a positive result, sensitivity increased to 53%; false positive cases of GI reduced PPV to 80%, while specificity (98%) and NPV (95%) changed little. Considered alone, GI had the lowest sensitivity (25%) and PPV (65%). FNA was useful in this U.S. population with MI, identifying almost half the affected patients. However, nondiagnostic results, such as granulomatous inflammation, should be interpreted with caution.