Nuclear grooves are longitudinal invaginations of the nuclear envelope bilayer, which constitute a characteristic feature of papillary thyroid carcinoma. Their pathogenesis is not yet clear, but there is evidence for the involvement of a signaling pathway downstream of the protooncogene RET. The presence of nuclear grooves is not specific for papillary thyroid carcinoma because it has been documented in other types of thyroid neoplasms, in nonneoplastic thyroid lesions, in ovarian neoplasms (Brenner, adult granulosa cell, and transitional cell tumors), in breast carcinomas, in cervicovaginal and endometrial smears, in papillary neoplasms of several organs (such as papillary transitional cell carcinoma of the bladder, papillary renal cell carcinoma, papillary endometrioid carcinoma of the prostate), in thymic carcinomas, and in nonepithelial tumors.