Background: Aim of the study was the biological characterization of melanoma metastases. Material and Methods: 27 patients with metastatic malignant melanoma (MM) were examined with PET and the radiotracers 18F-2-deoxy-D-glucose (FDG) and lsO-labeled water to determine metabolism and perfusion of the metastases. Results: The PET-FDG scans 60 min post injectionem (p. i.) showed a higher FDG accumulation in the metastases in comparison to normal tissue. No significant difference was noted in the perfusion of the metastases as measured with 150-labeled water in comparison to normal tissue. Therefore, perfusion is not adequate for tumor differentiation. There was no correlation between the FDG uptake values 60 min p. i. and the perfusion values 5 min p. i. of the metastases (r = 0.2577). No correlation resulted from the FDG uptake values and the period between MM diagnosis and death (r =-0.468) and the period between PET examination and death (r = 0.0427). Furthermore, we were able to distinguish between two main groups differing in the primary tumor type: nodular melanoma (MM) or superficial spreading melanoma (SSM) followed from all patient data. The FDG uptake values were compared and showed a distinct higher uptake value of NM metastases in comparison to SSM metastases. Finally the comparison of functional PET data to clinical data showed a high positive value in differentiation of malignant tissue and normal tissue. Conclusion: The radioactively labeled tracer 2-deoxy-D-glucose is an important substance for primary tumor diagnosis as well as for differentiation of malignant processes and normal tissue. The clinical value of PET for the optimization of tumor diagnosis, tumor staging as well as for therapy monitoring must be evaluated in a larger number of patients.