Oncocytic cell represents a special phenotype of neoplastic cells reflecting a unique biologic process characterized by the huge proliferation of morphologically abnormal mitochondria in the cytoplasm of neoplastic cells. This phenotype is driven by quite specific molecular mechanisms that interfere with mitochondrial function and metabolism. The oncocytic phenotype is more common in tumors arising in tissues presenting low proliferative rate, such as thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands, and it is superimposed on the genotypic and conventional histologic features of the tumors. In this short review, we address the similarity of the molecular alterations and of the biological features of the neoplastic cells in the oncocytic tumors of the different organs. We also discuss the differential diagnosis of benign and malignant oncocytic tumors as well as the prognosis of the malignant ones. We conclude that this rather unique phenotype, which is observed in tumors from different organs, indicates common metabolic alterations that may represent a useful target for therapeutic purposes.