Italy, home to one of the world’s oldest populations, has traditionally shown geographic differences in cancer incidence, with rates decreasing from north to south. The cancer registries that have been accredited by the Italian Cancer Registry Network (AIRTUM), during the last 20 years altogether cover the 90 % of the Italian population, aiming to improve data quality, standardize procedures, and promote research. This study presents the methodological approaches used for data collection, quality control, and analysis to describe current patterns of cancer incidence, mortality, and survival across Italy's three macro-areas (North, Central, South). Estimates of incidence rates and case numbers for 2025 were also produced. Data from 34 accredited cancer registries were analyzed, comprising over 4.6 million cases from 1981 to 2020, with a detailed focus on the 2008–2017 period, which includes over 3 million cases. Cancer incidence and mortality data were collected according to ICD-O-3 and ICD-10 classifications and processed for statistical analysis using tools such as SEERPrep, SEERStat, and the Joinpoint Regression Program. Age-standardized rates were calculated, and incidence and mortality trends from 2013 to 2017 were modeled. Five-year cumulative net survival was estimated using the Pohar-Perme method to adjust for competing risks. Survival trends were analyzed by geographic areas and cancer sites, revealing regional disparities in cancer outcomes.