A number of radiopharmaceutical agents have been evaluated for the detection of malignant melanoma. Because anamine is necessary for melanin synthesis, melanotic tumors may possess numerous amine receptors. Tc-99m HMPAO consists of macrocyclic amine radicals. The purpose of this study was to evaluate Tc-99m HMPAO as an effective agent for localizing malignant melanomas on the radioisotope imaging. Six patients, with malignant melanomas were studied. Tc-99m HMPAO SPECT images were obtained in all patients. SPECT was used for the localization of the primary focus, and whole body scans were used for the evaluation of unexpected metastatic lesions. The results were compared with MRI and CT. Tc-99m HMPAO SPECT revealed a high correlation with CT and MRI for the primary focus. Abnormally increased activity at the unexpected metastatic lymph nodes in two patients were also noticed. This was confirmed by CT and MRI for those sites. Tc-99m HMPAO appears to be a useful agent for the localization of both the primary focus and unexpected metastatic lesion in patients with malignant melanoma.