To comparatively evaluate the lesion-detecting ability of 2-[18F]FDG total-body PET/CT (TB PET/CT) and conventional digital PET/CT. This study enrolled 67 patients (median age, 65years; 24 female and 43 male patients) who underwent a TB PET/CT scan and a conventional digital PET/CT scan after a single 2-[18F]FDG injection (3.7MBq/kg). Raw PET data for TB PET/CT were acquired over the course of 5min, and images were reconstructed using data from the first 1, 2, 3, and 4min and the entire 5min (G1, G2, G3, G4, and G5, respectively). The conventional digital PET/CT scan acquired in 2-3min per bed (G0). Two nuclear medicine physicians independently assessed subjective image quality using a 5-point Likert scale and recorded the number of 2-[18F]FDG-avid lesions. A total of 241 lesions (69 primary lesions; 32 liver, lung, and peritoneum metastases; and 140 regional lymph nodes) among 67 patients with various types of cancer were analyzed. The subjective image quality score and SNR (signal-to-noise ratio) increased gradually from G1 to G5, and these values were significantly higher than the values at G0 (all p < 0.05). Compared to conventional PET/CT, G4 and G5 of TB PET/CT detected an additional 15 lesions (2 primary lesions; 5 liver, lung, and peritoneum lesions; and 8 lymph node metastases). TB PET/CT was more sensitive than conventional whole-body PET/CT in detecting small (4.3mm, maximum standardized uptake value (SUVmax) of 1.0) or low-uptake (tumor-to-liver ratio of 1.6, SUVmax of 4.1) lesions. This study explored the gain of the image quality and lesion detectability of TB PET/CT, compared to conventional PET/CT, and recommended the appropriate acquisition time for TB PET/CT in clinical practice with an ordinary 2-[18F] FDG dose. • TB PET/CT increases the effective sensitivity to approximately 40 times that of conventional PET scanners. • The subjective image quality score and signal-to-noise ratio of TB PET/CT from G1 to G5 were better than those of conventional PET/CT. • 2-[18F]FDG TB PET/CT with a 4-min acquisition time at a regular tracer dose detected an additional 15 lesions compared to conventional PET/CT.