Cutaneous squamous cell carcinoma (cSCC), the most common cancer capable of metastasis, has variable reported metastatic rates and the impact of individual risk factors for metastasis is unknown. This study examined pathology records of excised cSCC over a 10-year period. Uni-variate and multi-variate analyses including patient demographics, maximum clinical diameter (MCD), anatomical sub-site, histological differentiation, perineural invasion (PNI), and lymphovascular invasion (LVI) of the lesion were performed. The primary endpoint was time to metastasis. Six thousand one hundred sixty four patients (median age 74 years) underwent excision of 8,997 primary cSCC. During the median follow-up of 70 months, the metastatic rate of cSCC was 1.9-2.6%. Multi-variate analysis showed that MCD (hazards ratio 1.41 [95% CI 1.25-1.60] P < 0.001), PNI (5.29; P < 0.0001), poor histological differentiation (4.26; P < 0.0001), location in the ear and retro-auricular area (3.31 [1.17-9.33]; P = 0.0024), cheek (3.18 [1.15-8.81]; P = 0.026), and lip (4.84; P = 0.009) increased the risk of metastasis. We show a 1.9-2.6% metastatic rate for cSCC with MCD, histologic differentiation, PNI, and certain anatomical sub-sites being independent risk factors for metastasis. A prospective study on our proposed risk stratification scheme based on these parameters may lead to identification of high-risk lesions that would benefit from more intensive treatment and/or routine post-operative follow-up.Inc. Copyright © 2012 Wiley Periodicals, Inc.