Background The thyroid gland is a treasure trove of pathology ranging from the benign to the overtly malignant. Both neoplastic and non-neoplastic thyroid lesions can exhibit oncocytic change. Here we present an overview of cytologic, and histopathologic findings encountered in these oncocytic neoplasms with a focus on the molecular aspects that drive their tumorigenesis. Summary Oncocytic change is unique to a subset of thyroid lesions ranging from non-neoplastic nodular hyperplasia to high-grade malignancy. It can also be encountered in non-follicular derived neoplasms as well as in the adjacent parathyroid glands. At the genetic level, these lesions demonstrate a different genetic signature from classic follicular-derived lesions, often involving alterations of mitochondrial genes.