Paired box protein Pax-8 (PAX8) is a member of the PAX family of transcription factors. It is essential for organogenesis during embryonic development of the kidney, thyroid and paramesonephric ducts, giving rise to the urogenital organs including the seminal vesicles, vas deferens, ureter, uterus, and fallopian tubes. Although PAX8 is crucial for organogenesis, sustained expression in the normal kidney, thyroid, breast, seminal vesicles, ovarian, cervical, and endometrial epithelia suggest a role for homeostatic control of mature tissues. Immunohistochemical staining revealed almost exclusive nuclear localization, with low or negligible cytoplasmic expression.  Due to the restrictive expression in normal tissues, PAX8 has been suggested to be a sensitive and specific marker for both primary and metastatic tumors derived from the above mentioned organs and tissues. PAX8 is expressed in renal cell carcinoma of clear cell, papillary and chromophobe subtypes. It is also found in endometrioid carcinoma, serous carcinoma, and thyroid carcinomas. However, PAX8 expression in lymphoid tissue has been controversial. The N-terminal polyclonal PAX8 antibody was found to cross-react with PAX5; previous data suggesting the use of PAX8 for diagnosis of malignant lymphomas should be re-evaluated. The cause may be due to a substantial sequence homology in the N-terminus of PAX8 and PAX5 (70%).