Description: 18 F-FDG PET/CT has been proven to be a highly sensitive method for pheochromocytomas/paragangliomas (PHEOs/PGLs) associated with succinate dehydrogenase (SDH) mutations. This finding has been attributed to altered tumor cell metabolism resulting from these mutations and does not provide additional prognostic information to genotype. Therefore, identification of new biomarkers for aggressiveness is needed. A high Ki-67 index was proposed to be an additional prognostic factor. This pilot study aimed to evaluate 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT) PET/CT, a PET proliferation tracer, as a potential imaging agent in a series of 12 PHEO/PGL patients with different genetic backgrounds, to compare 18 F-FLT uptake with 18 F-FDG PET/CT, and to evaluate classic factors of aggressiveness. Methods: Twelve patients (7 metastatic and 5 nonmetastatic) were prospectively evaluated with 18 F-FDG and 18 F-FLT and followed for at least 2 y after the initial imaging work-up. Uptake was assessed at a lesion level, visually and quantitatively by maximum standardized uptake values (SUV max ) for both tracers. 18 F-FLT uptake was compared with risk factors known to be linked with a poor prognosis in PGLs ( SDHB -mutated status, lesion size, dopaminergic phenotype) and with 18 F-FDG uptake. Results: In 12 patients, 77 lesions were assessed. All lesions had low 18 F-FLT uptake (median SUV max , 2.25; range, 0.7–4.5). There was no apparent superiority of 18 F-FLT uptake in progressive lesions, and most of the lesions showed a mismatch, with high 18 F-FDG uptake (median SUV max , 10.8; range, 1.1–79.0) contrasting with low 18 F-FLT uptake. Conclusion: This study suggests that PHEOs/PGLs—even those that progress—do not exhibit intense 18 F-FLT uptake. It provides the first in vivo demonstration that proliferation may not be a major determinant of 18 F-FDG uptake in these tumors. These findings provide new insight into the biologic behavior of PGL and suggest that antiproliferative agents may be suboptimal for treatment of these tumors.