Purpose <p>This study aimed to retrospectively assess [¹⁸F]FDG PET/CT diagnostic accuracy in Kaposi Sarcoma (KS) patients.</p> Methods <p>All patients with KS who underwent [¹⁸F]FDG PET/CT in different clinical settings from January 2010 to December 2014 were analyzed retrospectively. [¹⁸F]FDG PET/CT positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and accuracy in KS patients were calculated on a per-patient based analysis. Furthermore, [¹⁸F]FDG PET/CT PPV, specificity, and accuracy for the final diagnosis of both KS and possible synchronous malignancies were evaluated.</p> Results <p>Eighteen consecutive HIV patients who underwent [¹⁸F]FDG PET/CT were retrospectively enrolled. Among them, fourteen patients showed a positive scan (14/18, 78%). False positive findings on [¹⁸F]FDG PET/CT images were brought about by synchronous malignancies (6/7) or inflammatory diseases (1/7). Four patients had a negative scan (4/18, 22%) without false negative cases. Consequently, sensitivity, specificity, PPV, NPV, and accuracy on a patient-based analysis were 100%, 36%, 50%, 100%, and 61%, respectively. Considering both KS and synchronous malignancies as true positive findings, specificity, PPV, and accuracy increased their value (80%, 93%, and 94%, respectively).</p> Conclusion <p>[¹⁸F]FDG PET/CT seems to be a valuable diagnostic tool in patients with KS. False positive findings such as synchronous primary tumors and inflammatory diseases could affect the accuracy of [¹⁸F]FDG PET/CT in the diagnosis of KS, even though their detection could have an impact on patient management. Prospective studies are needed, especially to compare [¹⁸F]FDG PET/CT with other diagnostic tools and to evaluate the possible implications for clinical management.</p>