Noninvasive methods for the bacteriological diagnosis of early-stage Mycobacterium ulcerans infection are not available. It was recently shown that fine-needle aspiration (FNA) could be used for diagnosing M. ulcerans infection in ulcerative lesions. We report that FNA is an appropriate sampling method for diagnosing M. ulcerans infection in nonulcerative lesions.Mycobacterium ulcerans infection (Buruli ulcer) is one of the 13 most neglected tropical diseases (9) and the third most common mycobacterial infection after tuberculosis and leprosy in immunocompetent humans (2,6,(13)(14). In general, this skin disease initially manifests as a painless nodule or papule, plaque, or edema (2). Without early intervention, these symptoms evolve into painless ulcers with undermined edges. The epidemiological, scientific, and management aspects of this disease have been well described (12). Over recent years, the management of Buruli ulcer patients has considerably changed with advances in antibiotherapy (3,5).Laboratory diagnosis of this mycobacterial infection is based on detection of acid-fast bacilli (AFB) through the direct examination of samples, isolation of mycobacteria by culture, histological analysis, and detection of M. ulcerans DNA by PCR (12). Ulcerative lesion specimens are collected using swabs (12). Swabbing from the undermined edges of ulcers may sometimes be difficult and painful. Collecting specimens from patients with nonulcerative lesions necessitates invasive procedures, such as incisional, excisional, or punch biopsies, which require hospital infrastructure not available in remote rural areas in Africa where M. ulcerans infection is endemic. Two studies recently reported that fine-needle aspirates could be used to diagnose M. ulcerans infection in ulcerative lesions. In both studies, the number of patients enrolled was not large enough to draw conclusions on the effectiveness of this technique in diagnosing nonulcerative forms.First, we compared the diagnostic sensitivities of fine-needle aspiration (FNA) and swabbing in 64 patients with ulcerative lesions. These patients had skin lesions consistent with active M. ulcerans infection, based on the clinical definition of the World Health Organization (12). For each patient with ulcerative lesions, two swab samples were taken from beneath the undermined edges of the ulcers and one FNA sample was taken from the edge of the lesion. The FNA procedure was similar to that described previously (4, 11); however, we used 20-gauge, 25-mm needles (attached to 5-ml syringes) instead of the 21-gauge and 23-gauge needles used in other studies. All samples were placed in sterile Venosafe tubes (Terumo) and sent, at room temperature, to the bacteriology unit of Angers University Hospital, France, within 7 days of collection for processing.Significant differences were observed in the efficacies of the two sampling methods. PCR using FNA samples detected M. ulcerans DNA in 56 of the 71 patients (diagnostic sensitivity of 79%), and PCR using swab samples detected M. ulcer...