How to diagnose and treat metastatic cervical lymph node cancer of unknown origin (a) Enlarged lymph nodes in the neck are a very common clinical sign and one of the common complaints of patients. Most of the swollen lymph nodes are confirmed to be benign, but some are diagnosed as metastatic cancer after pathology. What is the next step of treatment in this case? First, the primary clinical goal for metastatic cervical lymph node cancer of unknown origin is to find the primary site. Before the consultation process begins, the attending physician should have a thorough communication with the patient (or family) about the condition. Finding the primary lesion is the most important clinical goal for this type of disease, and this process may be very difficult, even some patients may not be able to find the primary lesion even after many tests (including expensive PETCT), so the doctor should inform the patient in advance about the difficulties and possible results of the examination process. Only when the patient and the doctor fully trust each other can clinical diagnosis and treatment proceed smoothly; second, medical history collection. Patients should provide as detailed medical history as possible, such as symptoms of upper respiratory tract and digestive tract, including sore throat, painful swallowing, difficulty in eating, hoarseness, shortness of breath, hearing loss, nasal blockage, nasal bleeding or blood in mucus, decreased sense of smell, headache, and other conditions. The attending physician should ask and record in detail whether there is a history of head and neck tumor or other parts of the body, including skin cancer, melanoma or thyroid cancer, and whether there is a history of radiation exposure, etc. Sometimes an unintentional symptom may be highly directional, which also requires the attending physician to have a keen clinical judgment; thirdly, a meticulous and comprehensive physical examination. The head and neck examination includes nasal cavity, ear canal, nasopharynx, oropharynx and hypopharynx. In addition to visual examination, the mouth and tongue root should be examined by palpation, which may cause discomfort to the patient; the scalp and neck skin, bilateral parotid glands, submandibular glands and thyroid gland should be examined; the lymph nodes in the neck should be examined, including the size, number and location. The whole body is examined including the chest, abdomen, breast, and even the groin. The physical examination should be meticulous. The author has encountered a case in which no lesion was found by nasopharyngoscopy, but later a suspicious lesion was found at the root of the tongue by palpation, and the nasopharyngoscopy was repeated and the primary lesion was found using a special modality. Therefore, no more expensive examinations can replace the meticulous and comprehensive physical examination by the attending physician; fourth, progressive ancillary examinations. Tests include cervical ultrasound, nasal endoscopy, nasopharyngoscopy, gastroscopy, chest radiograph, enhanced CT or MR, and even PET-CT, to name a few. The attending physician should prefer some tests according to the patient’s pathological type, site and differentiation of metastatic carcinoma in cervical lymph nodes, and consider further tests after the results are returned. Patients with suspicious lesions should be advised to undergo puncture or biopsy, and should never be given a one-time prescription to do so directly.