Multiple primary cancers are usually defined as primary malignant tumors of different histological origins in one person. Recently, there has been an increase in the number of patients diagnosed with multiple primary cancers. The study aims to evaluate the role of PET/CT in detecting second primary and subsequent tumors as well as to demonstrate the influence on the treatment management in patients with histologically proven synchronous or metachronous tumors. Fifty patients with clinically proven at least one malignancy have been evaluated and followed up for a year. Another inclusion criterion was a biopsy-proven additional primary synchronous (within 2-6 months after the first one) or metachronous (more than 6 months after the diagnosis of the first one) malignant tumor in a different organ. All patients were scanned on GE Discovery PET/CT 16 slices scanner from the top of the head to mid-thigh. The study was performed one hour after injection, using the weight-adjusted activity, hydration of patients with diuretic stimulation, and oral/i.v. contrast intake. Thirty out of 50 patients were females. The youngest patient was 25 years old, while the highest age was 84 years. Ten of the patients had third primary tumors and one patient had four different malignancies. Metachronous tumors were 2.4-fold higher than synchronous ones. The minimum time to detect a second tumor was 1 month, while the maximum was 15 years. As second malignancies we detected fourteen gastrointestinal cancers (28%), ten urogenital ones (20%), ten pulmonary tumors (20%), five breast cancers (10%), four lymphoma patients (8%), four head and neck squamous cell carcinomas (8%), two NET (4%), and one sarcoma (2%). As a result of the 18F-FDG PET/CT scan, the therapy plans of all 50 patients required modification at the minimum for the second tumor. 64% of the patients had multimodality therapy for their first cancer, which suggests that this approach could play an important role in the development of MPM. 81% of the additional malignancies in the female group, detected by PET/CT were in stages I or II, which provides a higher probability of cure. On the other hand, we detected advanced stage second primary disease in 70% of the patients in the male group. PET/CT can identify a significant number of additional primary neoplasms in patients with known primary cancer, acquiring combined metabolic and morphologic information, as well as its whole-body protocol. Integrated PET/CT can significantly modify the assessment of the tumor's dissemination and often change patient management substantially. Subsequent primary lesions identified after PET/CT scan are mainly in the early stage and thus have an excellent likelihood of being cured if treated promptly and aggressively.