Lung cancer is the leading cause of cancer-related mortality worldwide, and understanding its pathological patterns and trends is of interest for clinical and public health interventions. This study investigates the trends in lung cancer incidence rates from 1995 to 2021 in the Friuli Venezia Giulia (FVG) region in northeastern Italy, focusing on histological subtypes and sex-specific differences. Data were obtained from the population-based FVG Cancer Registry. Data on histological types of lung cancer were analyzed. Using census-based population estimates, age-standardized incidence rates (ASIRs) were calculated for three calendar periods (1995-2003, 2004-2012, 2013-2021). Joinpoint regression analysis was used to assess significant changes in trends, estimating annual percent change and average annual percent change (AAPC). A total of 24 519 lung cancer cases were recorded between 1995 and 2021, 70% in males. During 2013-2021, ASIRs were 31.9/100 000 males and 16.9/100 000 females. Adenocarcinoma accounted for the highest ASIRs in both sexes (15.2/100 000 males and 9.9/100 000 females). Over the 1995-2021 period, the overall incidence of lung cancer decreased in males (AAPC: -3.2%), whereas it increased in females (AAPC: +1.0%). Trends in adenocarcinoma were inconsistent for males but continued to rise in females. Squamous and small cell lung cancer incidence declined in males, while both increased in females. These trends underscore the importance of targeted prevention strategies, especially addressing smoking cessation in middle-aged females.