The present study investigated the potential value of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic features in estimating progression-free survival (PFS) and overall survival (OS) in patients affected by splenic marginal zone lymphoma. The estimated 2-year PFS and OS rates were 78% and 90%, whereas 5-year PFS and OS rates were 63% and 82%. Only lesion to liver maximum standardized uptake value ratio and lesion to blood-pool maximum standardized uptake value ratio were independent prognostic factors for PFS. By contrast, for OS, no positron emission tomography/computed tomography features were correlated with outcome. Introduction: Splenic marginal zone lymphoma (SMZL) is an indolent non-Hodgkin lymphoma usually with a good prognosis, but no clear metabolic behavior at fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ( F-18-FDG PET/CT). The aim of our analysis was to investigate the prognostic role of baseline F-18-FDG PET/CT parameters in SMZL. Materials and Methods: We retrospectively included 42 patients who received F-18-FDG-PET/CT before any treatments, and PET images were evaluated visually and semi-quantitatively by measuring lesion to liver (L-L) maximum standardized uptake volume (SUVmax) ratio (L-L SUV R), lesion to blood-pool SUVmax ratio ( L-BP SUV R), metabolic tumor volume, and total lesion glycolysis. Progression-free (PFS) and overall survival (OS) curves were plotted according to the Kaplan-Meier method. Results: In all patients, an increased splenic FDG uptake (higher than the background) was identified, showing the presence of diffuse spleen uptake in 35 patients and focal uptake in the remaining 7 patients. At a median follow-up of 51 months, relapse or progression of disease occurred in 23 patients with an average time of 38.1 months from the baseline F-18-FDG PET/CT, and death occurred in 4 patients with an average time of 26.8 months. The estimated 2-year PFS and OS rates were 78% and 90%, respectively, whereas 5-year PFS and OS rates were 63% and 82%, respectively. At multivariate analysis, only L-L SUV R and L-BP SUV R were independent prognostic factors for PFS. In addition, no significant association was discovered for OS, considering all features. Conclusions: L-L SUV R and L-BP SUV R were independently correlated with PFS. (C) 2020 Elsevier Inc. All rights reserved.