Basal cell carcinoma is the most common malignancy in Caucasian individuals. Metastatic basal cell carcinoma is extremely rare (with a rate estimated as 0.03%). Actin has been detected in aggressive forms of basal cell carcinoma, but their expression in metastatic lesions is not known. We compared the expression of actin and actin-related cytoskeletal proteins in relatively less aggressive basal cell carcinoma (nodular), aggressive basal cell carcinoma (infiltrative/morpheaform), and metastatic basal cell carcinoma. We studied 12 cases of nodular basal cell carcinoma, 10 cases of infiltrative basal cell carcinoma, and 10 cases of metastatic basal cell carcinoma with immunohistochemistry for alpha-smooth muscle actin, calponin, myosin, and E-cadherin. Expression was interpreted as positive when at least 5% of the tumor exhibited at least weak expression. Five of the ten patients with metastatic basal cell carcinoma had an antecedent history of radiotherapy. Actin was present in 3 of 12 (25%) of the nodular, all 10 of the infiltrative, and 3 of 10 of the metastatic basal cell carcinomas (P<0.05 for metastatic vs infiltrative and nodular vs infiltrative). Calponin was present in 50% of the nodular, 60% of the infiltrative, and 30% of the metastatic basal cell carcinomas (not statistically significant). Myosin expression was not detected in any of the cases. E-cadherin was present in 75% of the nodular, 70% of the infiltrative, and all of the metastatic basal cell carcinomas (P<0.05 for metastatic vs nodular). Our results suggest that increased actin may contribute to local invasiveness, but it is lost in the metastatic phenotype. History of previous radiotherapy may contribute to development of the metastatic phenotype.