Reed-Sternberg (R-S) cells are the main tumor cells of Hodgkin lymphoma (HL). HL has been reported to demonstrate a high level of [18F]2-fluoro-2-deoxy-D-glucose (FDG) uptake, but the determinant of FDG uptake for HL has not been well elucidated. Thus, we investigated the relationship of FDG uptake and the expressions of glucose transporter type 1 (Glut-1), glucose transporter type 3 (Glut-3), and hexokinase II (HK-II) in R-S cells of HL. There were 25 tissue-proven HL patients from January 2003 to July 2007 in our hospital. Of the 25 HL patients, 4 cases obtained by surgical excision were included in the present study. The immunostaining for Glut-1, Glut-3, and HK-II was conducted in the excised masses. The maximum standardized uptake values (maxSUVs) were compared to the expressions of Glut-1, Glut-3, and HK-II. Three HL patients (mixed cellularity = 2 and nodular sclerosis = 1) demonstrated moderate-strong expressions of Glut-1 in almost all R-S cells, and of these three HL patients, two underwent FDG-PET, which revealed a high level of maxSUVs (7.7, 6.5) in the corresponding HL lesions. One HL patient (lymphocyte depletion) showed weak Glut-1 expressions in only 10% of R-S cells, but no FDG-PET study was available. The expressions of Glut-3 and HK-II were various in all four HL patients, and no specific correlations with FDG uptake were found. In conclusion, high expressions of Glut-1 in R-S cells may play a crucial role for the high FDG uptake in Hodgkin lymphoma.