The incidence of cutaneous squamous cell carcinoma (SCC) in chronic lymphocytic leukemia (CLL) patients is significantly higher compared to age- and sex- matched controls.To evaluate the association of factors associated with SCC risk.Clinical CLL and SCC data were obtained from Mayo Clinic CLL resource and self-reported questionnaires among newly diagnosed CLL patients. We computed the CLL International Prognostic Index (CLL-IPI), from CLL prognostic factors, and a polygenetic risk score (PRS) from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Among 1269 CLL patients, the median follow-up was 7 years, and 124 patients subsequently developed SCC. Significant associations with SCC risk were history of skin cancer (HR=4.80,CI:3.37-6.83), CLL-IPI (HR=1.42,CI:1.13-1.80), and PRS (HR=2.58,CI:1.50-4.43). In a multivariable model, these factors were independent predictors (c-statistic=0.69,CI:0.62-0.76). T-cell immunosuppressive treatments was also associated with SCC risk (HR=2.29,CI:1.47-3.55, adjusted for age, sex, and prior SCC).Sample size decreases when combining all risk factors in a single model.SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high-PRS. Future studies should develop prediction models that include these factors to improved screening guidelines.