An oncocytic, also called “Hurthle cell lesion” (HCL), has been defined as “a discrete lesion composed mainly of oncocytic (Hurthle) cells. However, the percentage of Hurthle cells required for the lesion to be diagnosed as a HCL has been controversial. A distinction between neoplastic and nonneoplastic HCLs should be made in order to segregate patients for whom surgery is indicated (neoplastic) from those who may be managed conservatively (nonneoplastic). This chapter discusses the controversy of diagnosis of oncocytic/Hurthle cell lesion, whether it is neoplastic or nonneoplastic. It provides, with illustrations, the characteristic cytological features of both neoplastic and nonneoplastic HCLs. In addition, this chapter explores the possible role of molecular biology in reaching the proper diagnosis and accordingly, the appropriate management.