Background: Investigation of the clinical feasibility of dynamic whole-body (WB) [18F]FDG PET, including standardized uptake value (SUV), rate of irreversible uptake (Ki), and apparent distribution volume (Vd) in physiologic tissues, and comparison between inflammatory/infectious and cancer lesions. Methods: Twenty-four patients were prospectively included to undergo dynamic WB [18F]FDG PET/CT for clinically indicated re-/staging of oncological diseases. Parametric maps of Ki and Vd were generated using Patlak analysis alongside SUV images. Maximum parameter values (SUVmax, Kimax, and Vdmax) were measured in liver parenchyma and in malignant or inflammatory/infectious lesions. Lesion-to-background ratios (LBRs) were calculated by dividing the measurements by their respective mean in the liver tissue. Results: Seventy-seven clinical target lesions were identified, 60 malignant and 17 inflammatory/infectious. Kimax was significantly higher in cancer than in inflammatory/infections lesions (3.0 vs. 2.0, p = 0.002) while LBRs of SUVmax, Kimax, and Vdmax did not differ significantly between the etiologies: LBR (SUVmax) 3.3 vs. 2.9, p = 0.06; LBR (Kimax) 5.0 vs. 4.4, p = 0.05, LBR (Vdmax) 1.1 vs. 1.0, p = 0.18). LBR of inflammatory/infectious and cancer lesions was higher in Kimax than in SUVmax (4.5 vs. 3.2, p < 0.001). LBRs of Kimax and SUVmax showed a strong correlation (Spearman’s rho = 0.83, p < 0.001). Conclusions: Dynamic WB [18F]FDG PET/CT is feasible in a clinical setting. LBRs of Kimax were higher than SUVmax. Kimax was higher in malignant than in inflammatory/infectious lesions but demonstrated a large overlap between the etiologies.