OBJECTIVE To characterize clinical presentation and prognostic factors in patients with histologically proven regional lymph node metastasis from cutaneous squamous cell carcinoma of head and neck origin. METHODS Retrospective, nonrandomized case series. METHODS Tertiary referral center. METHODS Forty-five patients treated between 1984 and 1995 with regional metastatic squamous cell carcinoma of cutaneous head and neck origin. METHODS Forty-one patients underwent neck dissection (20 with parotidectomy) and 4 patients underwent parotidectomy alone. Thirty-six patients (80%) received postoperative radiation therapy with a mean dose of 60 Gy (range, 34-71 Gy). METHODS Recurrences and survival by univariate analysis using the Kaplan-Meier product-limit method. The log-rank test was used to evaluate prognostic significance of clinical variables. RESULTS Follow-up ranged from 2 months to 10 years (mean, 21 months). Compared with historical controls, a greater percentage of patients in our population with regional lymph node metastasis had primary lesions greater than 2 cm in diameter and 4 mm deep. Overall 2- and 5-year survival rates were 33% and 22%, respectively, while 5-year disease-free survival rate was 34%. Clinical staging of the neck proved to be the only factor of prognostic value (P<.01). Treatment failures occurred in 22 patients. CONCLUSIONS For the small subset of patients with regional metastasis from cutaneous squamous cell carcinoma, survival remains poor despite multimodality treatment. Clinical stage of the neck was the only factor that predicted outcome.