In a prospective study of 178 patients with malignant melanoma, a subset of 33 patients (18.5%) was identified to be at significantly higher risk for developing metastatic disease based on history of cigarette smoking. Patients in this high-risk group (current smokers with a greater than 15 pack-years of smoking history) had two-year disease-free survival rates of 74.2%. versus 92.3% for the remaining patients (p = 0.008). A possible explanation of this phenomenon is that chronic smoking diminishes host defense mechanisms and results in an adverse affect on the biologic behavior of established malignant melanomas.