Population-based skin cancer screening is currently not recommended owing to lack of data to quantify the balance of benefits and harms. To compare thickness-specific incidence of melanoma in screened vs unscreened patients following the initiation of a primary care-based skin cancer screening initiative. This observational study of a quality improvement initiative was conducted from January 1, 2014, through December 31, 2018, among patients 35 years and older presenting for a primary care visit at primary care practices within an academic and community-based health care system during the study period. Data analysis was performed January 2020 to January 2022. Primary care clinicians were offered training in melanoma identification through skin examination and encouraged to offer annual screening to patients 35 years and older. Thickness of melanomas diagnosed in screened and unscreened patients. Among 595 799 analyzed screen-eligible patients, 144 851 (24.3%) were screened at least once. Screened patients were older (median [IQR] age, 59 [49-67] vs 55 [45-66] years) and more likely to be female (82 244 [56.8%] vs 250 806 [55.6%]; P < .001) and non-Hispanic White (124 747 [86.1%] vs 375 890 [83.4%]; P < .001) than unscreened patients. After adjusting for age, sex, and race, screened patients were more likely than unscreened patients to be diagnosed with in situ (incidence, 30.4 vs 14.4; hazard ratio [HR], 2.6; 95% CI, 2.1-3.1; P < .001) or thin invasive (≤1 mm) melanoma (incidence, 24.5 vs 16.1; HR, 1.8; 95% CI, 1.5-2.2; P < .001). Screened patients were also more likely than unscreened patients to be diagnosed with in situ (incidence, 26.7 vs 12.9; HR, 2.1; 95% CI, 1.7-2.6; P < .001) or thin invasive (≤1 mm) interval melanomas (melanoma diagnosed at least 60 days after initial screening examination) (incidence, 18.5 vs 14.4; HR, 1.3; 95% CI, 1.0-1.7; P = .03). Incidence of melanoma thicker than 4 mm in unscreened and screened patients, respectively, was 3.3 and 2.7 (HR, 0.8; 95% CI, 0.4-1.4; P = .38) for all melanomas and 2.7 and 1.5 (HR, 0.6; 95% CI, 0.2-1.2; P = .15) for interval melanomas. In this quality improvement study, primary care-based melanoma screening was associated with increased detection of thin melanoma, raising concern about overdiagnosis. Further studies with longer follow-up are needed to determine the influence of screening on the incidence of thick melanoma and outcomes associated with high costs and poor outcomes, such as metastasis.