INTRODUCTION: This retrospective follow-up study evaluates patient outcomes and treatment costs in two cohorts of incident NSCLC patients recorded in the population-based cancer registry of the Veneto Region in 2017 and 2019. METHODS: This study examines two cohorts of incident NSCLC patients recorded by the Regional Veneto cancer registry in 2017 (493 patients) and 2019 (557 patients). Cancer patients were followed for three years after diagnosis to assess the disease's outcomes and analyze the overall treatment-related costs. Overall survival and cancer-specific mortality were evaluated using Cox regression models. The log-transformed overall treatment costs for the 3 years following diagnosis were analyzed using linear regression. RESULTS: The overall mortality risk significantly lowered in the 2019 cohort (HR 0.84; 95% CI 0.72-0.98, = 0.024). Stage III patients were not associated with a significant overall survival rate (HR 0.71; 95% CI 0.50-1.02; = 0.065) but were associated with significantly higher cancer-specific survival (HR 0.61; 95% CI 0.41-0.91; = 0.015). Overall, the 2019 cohort showed significantly higher costs (coefficient 0.16; 95% CI 0.02-0.30, = 0.025), particularly as a result of increases in the costs of drug administration, outpatient services, and medical devices. However, during the same 3-year follow-up period, this cohort featured lower average costs for hospice care and hospitalizations. CONCLUSIONS: These results revealed notable differences in clinical outcomes and patient-related costs in incident NSCLCs in 2017 and 2019. The study highlights the importance of monitoring clinical outcomes and management costs in real-world oncology practice.