This study explores the efficacy of fine-needle tissue aspiration biopsy in the diagnosis of soft tissue infections that cannot be sampled satisfactorily by regular microbiological techniques. Aspiration biopsy was performed on 50 patients with presumptive soft tissue infections. The conditions investigated were decubitus, diabetic, ischemic, venous, and traumatic ulcers (2, 6, 1, 2, and 7 patients, respectively), cellulitis (23 patients), chronic osteomyelitis (5 patients), and infected surgical wounds (4 patients). Where possible, comparison with superficial cultures was made. All of the cultures obtained from aspirate samples taken from ulcers, chronic osteomyelitis, and infected surgical wounds were positive. In cellulitis, cultures from aspirates were positive in 30 and 81% of the cases, respectively, depending on the presence of concomitant antimicrobial therapy. These results suggest that fine-needle deep tissue aspiration biopsy is reliable and clinically applicable for deep tissue sample collection. The procedure is simple, brief, and does not cause significant discomfort to the patient. It also plays an important role in providing a guideline for antimicrobial therapy.