Introduction Accurate diagnosis of multiple myeloma (MM) and related disorders depends on imaging studies for lesion detection, which is crucial for treatment planning. The 18F-fluorodeoxyglucose (FDG) PET imaging system is well-established, with high sensitivity and specificity in identifying myeloma lesions. Additionally, 11C-acetate serves as an effective radiotracer for detecting MM lesions. Metabolic tumor volume (MTV) measured with 18F-FDG PET has been suggested as a prognostic factor in MM patients. This study aimed to compare the feasibility of measuring MTV in patients with myeloma-related diseases using 11C-acetate or 18F-FDG PET/CT. Methods We retrospectively reviewed six patients with MM - three with symptomatic MM and three with smoldering MM - and one patient with a myeloma-related disorder, all of whom underwent both 11C-acetate and 18F-FDG PET/CT scans. Using a dedicated workstation (PET-STAT; AdIn Research, Inc., Tokyo, Japan) equipped with a standardized uptake value (SUV)-based automated contouring program, we calculated the SUV for MTV. Bone areas with an SUV above thresholds of 2.0 or 2.5 were grouped accordingly. Results MTV detection in the whole body was significantly higher with 11C-acetate compared to 18F-FDG at both thresholds. For the 2.5 threshold, MTV was 129 ± 109 mL versus 3.93 ± 9.38 mL (p = 0.016), and for the 2.0 threshold, it was 316 ± 221 mL versus 12.1 ± 23.7 mL (p = 0.016). Conclusions MTV measurements were significantly higher in PET/CT using 11C-acetate compared to 18F-FDG. This finding highlights the potential superiority of 11C-acetate over 18F-FDG for assessing the MTV of lesions in patients with MM.