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Rationale: To evaluate the detection rate of incidental second primary neoplasms in patients with prostate cancer on 18F-Fluciclovine PET/CT. Methods: Imaging reports and patient demographic data were retrospectively reviewed from 663 clinical 18F- Fluciclovine PET/CT studies, performed in 601 patients for the assessment of their prostate cancer (643 - recurrence evaluation, 20 - initial staging) from August 2016 to April 2021. Maximum standardized uptake value (SUVmax) of the suspected second neoplasms was determined. The results of 18F- Fluciclovine PET/CT were correlated with clinical and radiological studies to determine the nature of the suspected second neoplasms. Results: Fifty-five patients (9.1%) had findings suspicious for a second neoplasm. 39/55 had a known second malignancy diagnosis prior to the PET/CT. An incidental second primary neoplasm was first suspected on 18F- Fluciclovine PET/CT in 16/601 patients (2.7%). Three of the sixteen patients had PET/CT suggestive of a meningioma that was corroborated on magnetic resonance imaging (MRI). Of the remaining 13 patients, 11 had a tissue diagnosis confirming a malignancy. Second malignancies included renal cell carcinoma (RCC; 5/11; 45.5%), urothelial carcinoma (n = 2), multiple myeloma, chondrosarcoma, cutaneous squamous cell carcinoma, squamous cell carcinoma of the esophagus and lung (n = 1, each; except for one patient with both esophageal and lung carcinomas). Among histopathologic confirmed malignancies, clear-cell RCC had the lowest uptake (SUVmax 3.4), and cutaneous squamous cell carcinoma had the highest uptake (SUVmax 13.6). Of the two patients with no histopathologic confirmation, one had ultrasound and MRI findings corroborating the diagnosis of RCC. The other patient had a solitary lung nodule suspicious for primary lung carcinoma and elected to undergo observation. Conclusion: Incidental findings consistent with a second primary neoplasm are not infrequently seen on 18F- Fluciclovine PET/CT performed for assessment of prostate cancer (9.1%). Of the incidentally detected primary cancers, RCC was the most common (45.5%). These findings indicate the need for a careful analysis of 18F-Fluciclovine PET/CT images, due to the broad tumor imaging capabilities of this radiotracer.