The incidence rates of keratinocyte cancer are increasing globally; however, the incidence rates of cutaneous squamous cell carcinoma (cSCC) in situ and the risk of developing subsequent invasive cSCC remain unknown. To estimate annual population-based age-standardized incidence rates of histopathologically confirmed cSCC in situ stratified by sex, age, and body site and to assess the risk of developing invasive cSCC among patients with cSCC in situ compared with the general population. This nationwide epidemiological population-based cohort study used cancer registry data to identify all patients with a first incident of histopathologically confirmed cSCC in situ between January 1, 1989, and December 31, 2017. In addition, all patients with cSCC in situ who subsequently had a first incident of invasive cSCC were identified up to June 11, 2019. Data were analyzed between March 18 and November 12, 2019. Age-standardized incidence rates per year for cSCC in situ, standardized to the 2013 edition of the European Standard Population, were calculated by sex, age, and body site. Cumulative risks, standardized incidence ratios, and absolute excess risks were calculated to assess the risk of invasive cSCC in patients with cSCC in situ compared with the general population. In this population-based cohort study of 88 754 patients with a first incident of cSCC in situ between January 1, 1989, and December 31, 2017, 58.8% were women; the median age was 75 years (interquartile range [IQR], 67-82 years) for women and 73 years (IQR, 65-80 years) for men. Increasing incidence rates were observed, with the highest incidence rates in 2017 among women in general (71.7 cases per 100 000 person-years) and among men 80 years and older (540.9 cases per 100 000 person-years). The most common body site among women was the face (15.9 cases per 100 000 person-years) and among men was the scalp and/or neck (12.3 cases per 100 000 person-years). After 5 years of follow-up, among patients with cSCC in situ, the cumulative risk of developing an invasive cSCC at any anatomic location was 11.7% (95% CI, 11.6%-11.9%) in men and 6.9% (95% CI, 6.8%-7.0%) in women (P < .001). The standardized incidence ratio was highest in the first year of follow-up among both men (16.6; 95% CI, 15.7-17.5) and women (15.1; 95% CI, 14.2-16.1). This study reports the first nationwide incidence rates of cSCC in situ to date. The increasing incidence rates of cSCC in situ and the high risk of developing invasive cSCC among patients with cSCC in situ may increase the health care burden associated with precursors of keratinocyte cancer and highlight the need to include cutaneous skin cancer precursor lesions when exploring policies to address skin cancer care.