BackgroundNeuroendocrine malignancies of the prostate represent a spectrum of diseases. Treatment-induced neuroendocrine differentiation (tiNED) in hormonally treated adenocarcinoma has been the subject of a large amount of recent research. However, the identification of neuroendocrine features in treatment-naïve prostatic tumor raises a differential diagnosis between prostatic adenocarcinoma with de-novo neuroendocrine differentiation (dNED) versus one of the primary prostatic neuroendocrine carcinomas (P-NEC). This case series focuses on the recent advances made in the field of whole-body in-vivo molecular imaging of patients with prostatic neuroendocrine malignancies, using the PET-CT technology. While [18F]FDG is being used as the main PET radiotracer in oncologic imaging and reflects glucose metabolism of malignant lesions, other molecules labeled with positron-emitting isotopes, mainly somatostatin-analogues labeled with 68Ga and PSMA-ligands labeled with either 18F or 68Ga, have been extensively studied and are now routinely used in departments of nuclear medicine and molecular imaging.Case presentationWe present three cases of patients with different pathologically-proven entities within the spectrum of prostatic neuroendocrine malignancies: a patient with tiNED, a patient with dNED, and a patient with P-NEC. The patients underwent PET-CT with different radiotracers, and the molecular imaging data were helpful in guiding clinical decisions. We summarize and discuss relevant published data on each of the presented entities from clinical, biological and molecular imaging standpoints. We also provide the reader with practical recommendation regarding the preferred PET radiotracer for imaging each entity.ConclusionSeveral PET radiotracers are available to characterize and assess whole-body extent of prostatic malignancies within the neuroendocrine spectrum. Awareness to clinical, biologic and pathologic data should guide the selection of preferred PET radiotracer for imaging each entity. This review is unique being directed to basic scientists, clinicians, pathologists, radiologists and nuclear medicine physicians, representing the multidisciplinary nature of oncologic research nowadays.