The aim of this prospective study was to assess the diagnostic value of iodine-123-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide (IBZM) whole-body imaging in comparison to thallium-201 scintigraphy in patients with metastatic malignant melanoma. Ten patients with suspected or proven locoregional metastases of malignant melanoma underwent whole-body scintigraphy both with 201Tl and 123I-IBZM prior to scheduled surgery. Whole-body scans and planar scintigrams were acquired at 5 min and 30 min after injection of 100 MBq 201Tl and at 10 min, 2 h, 4 h and 24 h after injection of 185 MBq 123I-IBZM. Ten out of 12 melanoma metastases, both melanotic and amelanotic as proven histologically, were detected by 201Tl with a sensitivity of 83%. 123I-IBZM showed tracer uptake only in 3 melanotic metastases (sensitivity: 25%) with a maximum tumor-to-background ratio within 4 h, while none of the amelanotic metastases was IBZM-positive. All lesions localized by 123I-IBZM showed tracer uptake of 201Tl as well, while 201Tl-negative lesions were also negative with IBZM. Because of the poor results of IBZM, the study was terminated after an interim evaluation of 10 patients. 123I-IBZM is a tracer with only moderate sensitivity in melanotic melanoma lesions, suggesting that this method has no clinical value as a routine investigation in melanoma patients. In comparison, our previous results with 201Tl whole-body scintigraphy yielded a significantly higher sensitivity of about 80% in patients with locoregional melanoma metastases and may thus offer considerable potential in non-PET melanoma imaging.