Aim: The recent introduction of long axial field-of-view (LAFOV) PET/CT scanners has yielded very promising results regarding image quality and sensitivity in oncological patients. We, herein, aim to determine an appropriate acquisition time range for the new long axial field of view Biograph Vision Quadra PET/CT (Siemens Healthcare) using low dose [¹⁸F]FDG activity in a group of melanoma patients. Methodology: Forty-nine melanoma patients were enrolled in the study. All patients underwent total body PET/CT from the top of the head through the feet in two bed positions (field-of-view 106 cm) after i.v. injection of 2.0 MBq/kg [¹⁸F]FDG. The PET images of the first bed position (head to upper thigh; PET-10) were reconstructed and further split into 8-min (PET-8), 6-min (PET-6), 5-min (PET-5), 4-min (PET-4), and 2-min (PET-2) duration groups. Comparisons were performed between the different reconstructed scan times with regard to the visual evaluation of the PET/CT scans using the PET-10 images as reference and by calculating the 95%-CI for the differences between different time acquisitions. Moreover, objective evaluation of PET/CT image quality was performed based on SUV calculations of tumor lesions and background, leading to calculation of liver signal-to-noise ratio (SNR), and tumor-to-background ratio (TBR). Results: A total of 60 scans were evaluated. Concerning visual analysis, 49/60 (81.7%) PET-10 scans were pathological, while the respective frequencies were 49/60 (81.7%) for PET-8 (95%-CI: − 0.0602–0.0602), 49/60 (81.7%) for PET-6 (95%-CI: − 0.0602–0.0602), 48/60 (80%) for PET-5 (95%-CI: − 0.0445–0.0886), 46/60 (76.7%) for PET-4 (95%-CI: − 0.0132–0.1370), and 45/60 (75%) for PET-2 (95%-CI: 0.0025–0.1593). In 18 PET-10 scans, the extent of metastatic involvement was very large, rendering the accurate calculation of [¹⁸F]FDG-avid tumor lesions very complicated. In the remaining 42 PET-10 scans, for which the exact calculation of tumor lesions was feasible, a total of 119 tumor lesions were counted, and the respective lesion detection rates for shorter acquisitions were as follows: 97.5% (116/119) for PET-8 (95%-CI: 0–1), 95.0% (113/119) for PET-6 (95%-CI: 0–1), 89.9% (107/119) for PET-5 (95%-CI: 0–2), 83.2% (99/119) for PET-4 (95%-CI: 1–2), and 73.9% (88/119) for PET-2 (95%-CI: 2–4). With regard to objective image quality evaluations, as a general trend, the reduction of acquisition time was associated with a decrease of liver SNR and a decrease of TBR, although in lesion-based analysis the change in TBR and tumor SUV_mean values was non-significant up to 6 and 5 min acquisitions, respectively. Conclusions: In melanoma, low-dose LAFOV PET/CT imaging is feasible and can reduce the total scan time from head to upper thigh up to 5 min providing comparable diagnostic data to standard lengths of acquisition. This may have significant implications for the diagnostic work-up of patients with melanoma, given the need for true whole-body imaging in this type of cancer.