Cancers of unknown origin represent approximately 5% of all cancers and are therefore as frequent as some solid tumors such as gastric or pancreatic cancers. The diagnosis of cancer of unknown origin should be based on a detailed pathological examination including immunohistochemical techniques and electron microscopy; hormonal receptors should also be measured. Besides detailed medical history and physical examination, only a few additional tests should be carried out: routine chemistry including the assay of HCG, alphafoetoprotein and specific antigen of the prostate, chest X-ray, thyroid scan, mammography and abdominal CT scan. Other tests are generally not of sufficient specificity and sensitivity. Unknown primary tumors arising in the cervical area are frequently squamous cell carcinomas corresponding to occult primary tumors of the upper aerodigestive mucosae and are efficiently treated by cervicofacial radiotherapy or lymph node dissection. Women presenting with axillary lymph nodes with no obvious primary tumor should be treated according to the guidelines used for breast cancer. The patients with inguinal lymph nodes of unknown origin are usually treated with radiation therapy. The syndrome of germinal tumors of extragonadic origin corresponds to cases of undifferentiated or poorly differentiated carcinomas in patients under 50 years of age and with one of the following characteristics: involvement of the median organs, lung involvement, lymph node involvement or increase of alphafoetoprotein or HCG. The therapeutic approach recommended for these patients consists of the chemotherapeutic combination used for testicular cancer. For all other patients, the prognosis remains poor. Patients with local symptoms may be treated by radiation therapy; others may receive a combination of fluorouracil, doxorubicin and mitomycin.