ABSTRACT: BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is associated with underlying immunosuppression, so it may be a prognostic marker in patients with subsequent cancer. We therefore conducted a nationwide population-based Danish cohort study to evaluate whether a history of cutaneuos SCC has prognostic impact in patients with one of the following index cancers: non-Hodgkin's lymphoma (NHL), or cancer of the lung, colon, rectum, breast, or prostate. METHODS: We used Danish medical databases, which cover the entire Danish population of 5.6 million inhabitants and linked them using the unique personal identification number assigned to all Danish residents. From 1982 through 2003, we identified 745 index cancer patients with and 79,143 without previous cutaneous SCC. Using Cox proportional hazards regression, we calculated adjusted mortality rate ratios (MRRs) with 95% confidence intervals (CIs). RESULTS: Overall, previous SCC was associated with an increased mortality of cancer (MRR 1.13, 95% CI: 1.04-1.23). When examining index cancers separately, increased MRRs were found for cancer of the lung (MRR 1.23, 95% CI: 1.05-1.43), colon (MRR 1.13, 95% CI: 0.92-1.40), rectum (MRR 1.29, 95% CI: 1.00-1.67), breast (MRR 1.09, 95% CI: 0.82-1.43), and NHL (MRR 1.09, 95% CI: 0.81-1.47), but not for prostate cancer (MRR 0.99, 95% CI: 0.83-1.18). CONCLUSIONS: Our results suggest that previous cutaneous SCC is associated with poor prognosis of some cancers. This finding stresses the importance of adherence to the existing recommendations of screening, diagnosis, and treatment of cancer in patients with a history of SCC.