Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with (123)I-metaiodobenzylguanidine (MIBG), and (18)F-FDG PET. METHODS: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. RESULTS: The overall sensitivity of SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were (18)F-FDG PET-positive, of which 3 were also (123)I-MIBG scintigraphy-positive, giving a combined overall sensitivity of 96%. SRS also exceeded (123)I-MIBG scintigraphy and (18)F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. (123)I-MIBG scintigraphy was superior to (18)F-FDG PET for ileal neuroendocrine tumors, and (18)F-FDG PET was superior to (123)I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of (18)F-FDG PET (92%) exceeded that of both SRS (69%) and (123)I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. CONCLUSION: The overall sensitivity of (123)I-MIBG scintigraphy and (18)F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, (18)F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, (18)F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.