Cutaneous SCC is the second most common skin cancer among whites. Most cases of primary cutaneous SCC are induced by UV radiation. Chronic sun exposure is the major risk factor, and favored locations include the head and neck and other sun-exposed areas. Moreover, it is important for the clinician to recognize other risk factors associated with this malignancy, including HPV infection, occupational exposures, various genodermatoses, scarring dermatoses, chronic wounds, and burn scars. The allogenic transplant population is at most risk for developing cutaneous SCC. For these patients, aggressive patient education, control of immunosuppression, and clinical surveillance should be the standard of care. Most patients who have primary SCC have an excellent prognosis, and treatment is usually straightforward. A substantial minority of these neoplasms, however, may recur or metastasize. Obtaining a complete history and performing a total-body skin examination can help to identify tumors at high risk for recurrence or metastasis in addition to those that may be more easily treated. For those individuals with metastatic disease, however, the long-term prognosis is guarded. Based on recent reports, in the future, there may be a role in SLNB for cutaneous SCC to diagnose subclinical metastasis accurately. Larger studies and better guidelines need to be developed before SLNB can be routinely used in the management of metastatic disease. Physicians should emphasize to their patients the benefits of sun avoidance and protection from sunlight, beginning in childhood, to minimize the risk for developing this potentially life-threatening neoplasm.