Differentiation between in situ infection and simple tumor necrosis in cavitating lung tumors by means of imaging studies is difficult. In this study, we prospectively investigated the role of ultrasound (US)-guided transthoracic aspiration for bacteriologic examination of infected cavitating lung tumors, and the influence of the culture results on the treatment of patients. Twenty-two patients (18 men and four women) with cavitating lung tumors treated from January 1996 to October 1998 were included. All patients underwent US-guided transthoracic aspiration for bacterial, fungal, and mycobacterial cultures. Microorganisms were isolated from six of seven febrile patients and one of 15 nonfebrile patients. A total of nine pathogens were isolated from seven patients: Klebsiella pneumoniae (n = 3); Haemophilus influenzae (n = 2); Enterococcus faecium (n = 1); Bifidobacterium (n = 1); Shewanella putrefaciens (n = 1); and Mycobacterium tuberculosis (n = 1). Two pathogens were isolated from the aspirate cultures in two patients, while the others had monomicrobial infection. The six febrile patients who had positive lung aspirate cultures were treated with empiric antimicrobial agents before the culture results were available, and the culture results led to adjustment of the antibiotic regimen in five of these. The clinical conditions of the six patients with infected cavitating lung tumors improved after the initiation of individualized antimicrobial treatment. Pneumothorax occurred in one patient, and was the sole procedure-related complication. In conclusion, US-guided transthoracic aspiration is helpful for differentiating infected cavitating lung tumors from simple tumor necrosis. Infection in cavitating lung tumors is common among febrile patients, and the culture results can guide modification of the antimicrobial therapy.