In patients with chronic lymphocytic leukemia, squamous cell carcinoma behaves aggressively. Our purpose was to compare squamous cell carcinoma metastasis and mortality between patients with chronic lymphocytic leukemia and control subjects. Medical records were assessed retrospectively for 28 patients with chronic lymphocytic leukemia who underwent surgical excision of cutaneous squamous cell carcinoma and for 56 matched control subjects. The rate of metastasis and mortality from cutaneous squamous cell carcinoma were determined on a per-patient basis. Three of 28 patients with chronic lymphocytic leukemia had metastasis and died of metastatic disease. No metastases or deaths occurred among the 56 control subjects. Compared with control subjects, chronic lymphocytic leukemia patients with cutaneous squamous cell carcinoma were more likely to have metastasis (P = .0031) and die of metastasis (P = .0033). No significant association was detected between metastasis and history of chemotherapy administration for chronic lymphocytic leukemia. Among patients with chronic lymphocytic leukemia, surveillance for skin cancer and a decreased threshold for biopsy of suspect lesions are warranted.