Background: D842V PDGFRA mutation identifies a molecular subtype of GIST, primarly resistant to imatinib and characterized by higher indolent behavior and a prominent immune profile. Although functional imaging with ¹⁸FDG-PET plays a proven role in GIST, especially in early assessment tumor response, less is known about ¹⁸FDG-uptake according to the GIST molecular subtypes. Taking into account of clinical and molecular features of D842V mutant GIST, we assumed that this subset of GIST could also have a different ¹⁸FDG-uptake. Therefore, the aim of the present study has been to investigate the degree of FDG uptake of PDGFRA mutant GIST, focusing on D842V ones, in order to better define the role of functional imaging in this rare and peculiar subset of GIST. Methods: Patients with PDGFRA mutant GIST underwent ¹⁸FDG-PET were retrospectively included from seven GIST Italian reference centers. Data on maximum standardized uptake (SUVmax) value of primary tumor or metastatic disease were collected. Results: 71 patients have been included: 37 (55.1%) with D842V PDGFRA mutant GIST (group A) and 34 (47.9%) with PDGFRA non-D842V mutant GIST (group B). Additionally, 30 patients with exon 11 KIT mutant GIST have been included, as control (group C). SUVmax values were obtained from primary tumor and metastatic lesions in 55 (54,4%) and 46 (45,6%) patients, respectively. Considering the whole population of 101 patients, the global median SUVmax was 3,7 (IQR 0-9.1), while the median SUVmax for group A, B, and C was 0, 3.6, and 10.4, respectively. The median SUVmax of PDGFRA mutant GIST was significantly lower than the median value of exon 11 KIT mutant GIST (p < 0.001). Notably, median ¹⁸FDG-uptake was significantly lower in D842V PDGFRA mutant GIST compared to PDGFRA non-D842V mutant ones (p = 0.021). Conclusions: PDGFRA D842V-mutant GIST present an overall lower ¹⁸FDG uptake compared to other GIST subgroups. This feature could be related to their specific molecular background and is consistent with their higher tendency to an indolent behavior. Therefore, the role of functional imaging with ¹⁸FDG-PET in this subset of GIST is limited. Finally, the prognostic value of the ¹⁸FDG-uptake degree within all PDGFRA mutant GIST will be investigated in the future.