Many head and neck disease processes are manifest as neck masses. These conditions are treated by surgical excision except for some inflammatory masses, and often those too must be excised before a diagnosis can be made. The real question is when to excise the lesion to expedite treatment in the most cost-effective manner. In general, when signs of inflammation are associated with the mass, antibiotic treatment with short-term observation is acceptable. Persistence of the mass or an increase in mass size during observation mandates for their evaluation. Biopsy of a mass is considered for progressive growth, isolated nature or asymmetry of the mass, location (supraclavicular), development of symptoms associated with lymphoma (fever and hypertrophy of the spleen, liver, or Waldeyer's ring), or static size (if > 3 cm). In the adult patient, a complete head and neck physical examination is mandatory before biopsy. Needle biopsy of the neck mass is the current standard of care if no cause of the mass is found on examination. Identified benign cystic lesions or lymphomas indicate a need for excision, either as definitive treatment or for diagnostic reasons. If results of the needle biopsy are positive, equivocal, or even negative in the presence of a high index of suspicion for metastatic squamous cell carcinoma, an endoscopic examination is mandatory before open excision. If no discrete lesion is seen, guided biopsy of the upper aerodigestive tract is performed. Open biopsy of the mass should be accompanied by a frozen-section examination of the mass. A concomitant definitive neck dissection should be performed if the mass proves to be metastatic carcinoma.